A bone cement comprising an acrylic polymer mixture which is formulated to have a relatively high viscosity for a relatively long window, due to distributions of molecular weights and/or sizes of acrylic beads.

Patent
   9642932
Priority
Sep 14 2006
Filed
Sep 11 2007
Issued
May 09 2017
Expiry
Jul 23 2030
Extension
1046 days
Assg.orig
Entity
Large
9
959
currently ok
1. A cement kit, comprising:
(a) a liquid component including a monomer; and
(b) a powder component including polymeric beads,
in which the distribution of the molecular weight of the powder component is non-normal so that it is skewed to a higher molecular weight by introduction of higher molecular weight beads, the non-normal distribution of the molecular weight of the powder component causing (a) an increase in the immediate viscosity of a mixture of the liquid and powder components and compared with a cement having a substantially normal distribution, and (b) an increase in the length of the working window period in which the viscosity of the cement does not exceed 500 Pa.s compared with a cement having a substantially normal distribution.
2. A cement kit according to claim 1, in which the higher molecular weight beads have an average molecular weight of at least a factor of 2 of an average molecular weight of the polymeric beads.
3. A cement kit according to claim 2, in which the factor is at least 3.
4. A cement kit according to claim 3, in which the factor is at least 5.
5. A cement kit according to claim 1, further comprising a relatively small component including smaller sized beads.
6. A cement kit according to claim 1, wherein the polymeric beads comprise PMMA.
7. A cement kit according to claim 1, wherein the higher molecular weight beads have a molecular weight of about 600,000 Dalton to about 5,000,000 Dalton.
8. A cement kit according to claim 1, wherein the higher molecular weight beads have a molecular weight of about 3,000,000 to 4,000,000 Dalton.
9. A cement kit according to claim 1, wherein the higher molecular weight beads have a molecular weight of about 3,500,000 to 3,900,000 Dalton.
10. A cement kit according to claim 1, wherein an average molecular weight of the polymeric beads is about 130,000 to 170,000 Dalton.
11. A cement kit according to claim 1, wherein an average molecular weight of the polymeric beads is about 375,000 Dalton.

The present application claims the benefit under 119(e) of Ser. No. 60/825,609 filed Sep. 14, 2006, the disclosure of which is incorporated herein by reference.

The present application is related to U.S. patent application Ser. No. 11/461,072 filed on Jul. 31, 2006 and entitled “Bone Cement and Methods of Use Thereof”, which is a Continuation-in-Part of U.S. application Ser. No. 11/360,251 filed on Feb. 22, 2006, entitled “Methods, Materials and Apparatus for Treating Bone and Other Tissue” and is also a Continuation-in Part of PCT/IL2005/000812 filed on Jul. 31, 2005. The disclosures of these applications are incorporated herein by reference.

The present application is related to PCT application PCT/IL2006/052612 filed on Jul. 31, 2006 and entitled “Bone Cement and Methods of Use thereof” the disclosure of which is incorporated herein by reference.

The present application is also related to a series of U.S. provisional applications entitled “Methods, Materials and Apparatus for Treating Bone and Other Tissue”: Ser. No. 60/765,484 filed on Feb. 2, 2006; Ser. No. 60/762,789 filed on Jan. 26, 2006; Ser. No. 60/738,556 filed Nov. 22, 2005; Ser. No. 60/729,505 filed Oct. 25, 2005; Ser. No. 60/720,725 filed on Sep. 28, 2005 and Ser. No. 60/721,094 filed on Sep. 28, 2005. The disclosures of these applications are incorporated herein by reference.

The present application is related to PCT application PCT/IL2006/000239 filed on Feb. 22, 2006; U.S. provisional application Ser. No. 60/763,003, entitled “Cannula” filed on Jan. 26, 2006; U.S. provisional application Ser. No. 60/654,495 entitled “Materials, devices and methods for treating bones”. filed Feb. 22, 2005; U.S. Ser. No. 11/194,411 filed Aug. 1, 2005; IL 166017 filed Dec. 28, 2004; IL 160987 filed Mar. 21, 2004; U.S. Provisional Application No. 60/654,784 filed on Jan. 31, 2005; U.S. Provisional Application No. 60/592,149 filed on Jul. 30, 2004; PCT Application No. PCT/IL2004/000527 filed on Jun. 17, 2004, Israel Application No. 160987 filed on Mar. 21, 2004, U.S. Provisional Applications Ser. No.: 60/478,841 filed on Jun. 17, 2003; Ser. No. 60/529,612 filed on Dec. 16, 2003; Ser. No. 60/534,377 filed on Jan. 6, 2004 and Ser. No. 60/554,558 filed on Mar. 18, 2004; U.S. application Ser. No. 09/890,172 filed on Jul. 25, 2001; U.S. application Ser. No. 09/890,318 filed on Jul. 25, 2001 and U.S. application Ser. No. 10/549,409 entitled “Hydraulic Device for the injection of Bone Cement in Percutaneous Vertebroplasty filed on Sep. 14, 2005. The disclosures of all of these applications are incorporated herein by reference.

The present invention relates to bone cement, formulations thereof and methods of use thereof.

It is common to employ cement to repair bones in a variety of clinical scenarios.

For example, compression fractures of the vertebrae, which are a common occurrence in older persons, cause pain and/or a shortening (or other distortion) of stature. In a procedure known as vertebroplasty cement is injected into a fractured vertebra. Vertebroplasty stabilizes the fracture and reduces pain, although it does not restore the vertebra and person to their original height. In vertebroplasty the cement is typically injected in a liquid phase so that resistance to injection is not too great. Liquid cement may unintentionally be injected outside of the vertebra and/or may migrate out through cracks in the vertebra.

In another procedure, known as kyphoplasty, the fracture is reduced by expanding a device, such as a balloon inside the vertebra and then injecting a fixing material and/or an implant. Kyphoplasty reduces the problem of cement leakage by permitting a lower pressure to be used for injection of the cement.

In general, polymeric cements become more viscous as the polymer chain grows by reacting directly with the double bond of a monomer. Polymerization begins by the “addition mechanism” in which a monomer becomes unstable by reacting with an initiator, a volatile molecule that is most commonly a radical (molecules that contain a single unpaired electron). Radicals bond with monomers, forming monomer radicals that can attack the double bond of the next monomer to propagate the polymer chain. Because radicals are so transient, initiators are often added in the form of an un-reactive peroxide form which is stable in solution. Radicals are formed when heat or light cleaves the peroxide molecule. For applications in which high temperatures are not practical (such as the use of bone cement in vivo), peroxide is typically cleaved by adding a chemical activator such as N,N-dimethyl-p-toluidine. (Nussbaum D A et al: “The Chemistry of Acrylic Bone Cement and Implication for Clinical Use in Image-guided Therapy”, J Vasc Interv Radiol (2004); 15:121-126; the content of which is fully incorporated herein by reference).

Examples of commercially available viscous bone cements include, but are not limited to, CMW® Nos. 1, 2 and 3 (DePuy Orthopaedics Inc.; Warsaw, Ind., USA) and Simplex™-P and -RO (Stryker Orthopaedics; Mahwah, N.J., USA). These cements are characterized by a liquid phase after mixing and prior to achieving a viscosity of 500 Pascal-second. In a typical use scenario, these previously available cements are poured, while in a liquid phase, into a delivery device.

There have also been attempts to reduce cement leakage by injecting more viscous cement, for example, during the doughing time and the beginning of polymerization. However, the viscous materials, such as hardening PMMA, typically harden very quickly once they reach a high viscosity. This has generally prevented injection of viscous materials in orthopedic procedures.

Some bone fixing materials, such as polymethylmethacrylate (PMMA), emit heat and possibly toxic materials while setting.

U.S. patents and publication U.S. Pat. Nos. 4,969,888, 5,108,404, 6,383,188, Nos. 2003/0109883, 2002/0068974, U.S. Pat. Nos. 6,348,055, 6,383,190, 4,494,535, 4,653,489 and 4,653,487, the disclosures of which are incorporated herein by reference describe various tools and methods for treating bone.

US patent publication 2004/0260303, the disclosure of which is incorporated herein by reference, teaches an apparatus for delivering bone cement into a vertebra.

Pascual, B., et al., “New Aspects of the Effect of Size and Size Distribution on the Setting Parameters and Mechanical Properties of Acrylic Bone Cements,” Biomaterials, 17(5): 509-516 (1996) considers the effect of PMMA bead size on setting parameters of cement. This article is fully incorporated herein by reference.

Hernandez, et al., (2005) “Influence of Powder Particle Size Distribution on Complex Viscosity and Other Properties of Acrylic Bone Cement for Vertebroplasty and Kyphoplasty” Wiley International Science D01:10:1002/jbm.b.30409 (pages 98-103) considers the effect of PMMA bead size distribution on setting parameters of cement. Hernandez suggests that it is advantageous to formulate cement with a liquid phase to facilitate injection. This article is fully incorporated herein by reference.

U.S. Pat. No. 5,276,070 to Arroyo discloses use of acrylic polymers with a molecular weight in the range of 0.5 to 1.5 million Daltons in formulation of bone cement. The disclosure of this patent is fully incorporated herein by reference.

U.S. Pat. No. 5,336,699 to Cooke discloses use of acrylic polymers with a molecular weight of about one hundred thousand Daltons in formulation of bone cement. The disclosure of this patent is fully incorporated herein by reference.

A broad aspect of the invention relates to a bone cement characterized by a rapid transition from separate liquid monomer and powdered polymer components to a single phase characterized by a high viscosity when the components are mixed together with substantially no intervening liquid phase. Optionally, high viscosity indicates 500 Pascal-second or more. Mixing is deemed complete when 95-100% of the polymer beads are wetted by monomer. In an exemplary embodiment of the invention, mixing is complete in within 60, optionally within 45, optionally within 30 seconds.

In an exemplary embodiment of the invention, the cement is characterized by a working window of several minutes during which the viscosity remains high prior to hardening of the cement. Optionally, viscosity during the working window does not vary to a degree which significantly influences injection parameters. In an exemplary embodiment of the invention, viscosity increases by less than 10% during a sub-window of at least 2 minutes during the working window. Optionally, the viscosity in the working window does not exceed 500, optionally 1,000, optionally 1,500, optionally 2,000 Pascal-second or lesser or greater or intermediate values. In an exemplary embodiment of the invention, the working window lasts 6, optionally 8, optionally 10, optionally 15 minutes or lesser or greater or intermediate times. Optionally, ambient temperature influences a duration of the working window. In an exemplary embodiment of the invention, the cement can be cooled or heated to influence a length of the working window.

An aspect of some embodiments of the invention relates to formulations of bone cement which rely upon two, optionally three or more, sub-populations of polymer beads which are mixed with liquid monomer.

According to exemplary embodiments of the invention, sub-populations may be characterized by average molecular weight (MW) and/or physical size and/or geometry, and/or density. In an exemplary embodiment of the invention, size based and MW based sub-populations are defined independently. In an exemplary embodiment of the invention, the sub-populations are selected to produce desired viscosity characterization and/or polymerization kinetics. Optionally, the polymer beads comprise polymethylmethacrylate (PMMA) and/or a PMMA styrene copolymer. Optionally, PMMA is employed in conjunction with a methylmethacrylate (MMA) monomer.

Optionally, a high molecular weight sub-population contributes to a rapid transition to a high viscosity with substantially no liquid phase. Optionally, a low molecular weight subpopulation contributes to a longer working window.

Optionally, a sub-population with small size contributes to rapid wetting of polymer beads with monomer solution. In an exemplary embodiment of the invention, rapid wetting contributes to a direct transition to a viscous cement with substantially no liquid phase.

In some cases a small percentage of beads may not belong to any relevant sub-population. The small percentage of beads may be, for example 1%, 1.5%,2%, 3%, 4%, 5% or lesser or intermediate or greater percentages.

In one exemplary embodiment of the invention, there are at least two sub-populations of PMMA polymer beads characterized by molecular weights. For example, a first sub-population comprising 95 to 97% (w/w) of the total PMMA beads can be characterized by an average MW of 270,000-300,000 Dalton; a second sub-population (2-3% w/w) can be characterized by an average MW of 3,500,000-4,000,000 Dalton; and a third sub-population (0-3% w/w) can be characterized by an average MW of 10,000-15,000 Dalton.

In an exemplary embodiment of the invention, the polymer beads are characterized by a high surface area per unit weight. Optionally, the beads have a surface area of 0.5 to 1, optionally 0.5 to 0.8 optionally about 0.66 m2/gram or intermediate or lesser or greater values. Optionally, the high surface area/weight ratio improves wetting properties and/or shortens polymerization times, for example by contributing to polymer monomer contact.

In an exemplary embodiment of the invention, a cement characterized by an immediate transition to high viscosity is injected during a working window in a vertebroplasty or kyphoplasty procedure. Optionally, injection is under sufficient pressure to move fractured bone, such as vertebral plates of a collapsed vertebra. Optionally, injection of viscous cement under high pressure contributes to fracture reduction and/or restoration of vertebral height.

In an exemplary embodiment of the invention, the material (e.g., bone cement) includes processed bone (from human or animals origin) and/or synthetic bone. Optionally, the cement has osteoconductive and/or osteoinductive behavior. Additional additives as commonly used in bone cement preparation may optionally be added. These additives include, but are not limited to, barium sulfate and benzoyl peroxide.

According to some embodiments of the invention, a working window length is determined by an interaction between an immediate effect and a late effect. In an exemplary embodiment of the invention, the immediate effect includes MMA solvation and/or encapsulation of PMMA polymer beads. The immediate effect contributes to a high viscosity of the initial mixture resulting from solvation and/or friction between the beads. The late effect is increasing average polymer MW as the beads dissolve and the polymerization reaction proceeds. This increasing average polymer MW keeps viscosity high throughout the working window.

In an exemplary embodiment of the invention, a set of viscosity parameters are used to adjust a cement formulation to produce a cement characterized by a desired working window at a desired viscosity.

In an exemplary embodiment of the invention, there is provided a bone cement comprising an acrylic polymer mixture, the cement characterized in that it achieves a viscosity of at least 500 Pascal-second within 180 seconds following initiation of mixing of a monomer component and a polymer component and characterized by sufficient biocompatibility to permit in-vivo use.

Optionally, the viscosity of the mixture remains between 500 and 2000 Pascal-second for a working window of at least 5 minutes after the initial period.

Optionally, the working window is at least 8 minutes long.

Optionally, the mixture includes PMMA.

Optionally, the mixture includes Barium Sulfate.

Optionally, the PMMA is provided as a PMMA/styrene copolymer.

Optionally, the PMMA is provided as a population of beads divided into at least two sub-populations, each sub-population characterized by an average molecular weight.

Optionally, a largest sub-population of PMMA beads is characterized by an MW of 150,000 Dalton to 300,000 Dalton.

Optionally, a largest sub-population of PMMA beads includes 90-98% (w/w) of the beads.

Optionally, a high molecular weight sub-population of PMMA beads is characterized by an average MW of at least 3,000,000 Dalton.

Optionally, a high molecular weight sub-population of PMMA beads includes 2 to 3% (w/w) of the beads.

Optionally, a low molecular weight sub-population of PMMA beads is characterized by an average MW of less than 15,000 Dalton.

Optionally, a low molecular weight sub-population of PMMA beads includes 0.75 to 1.5% (W/W) of the beads.

Optionally, the PMMA is provided as a population of beads divided into at least two sub-populations, each sub-population characterized by an average bead diameter.

Optionally, at least one bead sub-population characterized by an average diameter is further divided into at least two sub-sub-populations, each sub-sub-population characterized by an average molecular weight.

Optionally, the PMMA is provided as a population of beads divided into at least three sub-populations, each sub-population characterized by an average bead diameter.

Optionally, the cement further includes processed bone and/or synthetic bone.

Optionally, the cement is characterized in that the cement achieves a viscosity of at least 500 Pascal-second when 100% of a polymer component is wetted by a monomer component.

Optionally, the viscosity is at least 800 Pascal-second.

Optionally, the viscosity is at least 1500 Pascal-second.

Optionally, the viscosity is achieved within 2 minutes.

Optionally, the viscosity is achieved within 1 minute.

Optionally, the viscosity is achieved within 45 seconds.

In an exemplary embodiment of the invention, there is provided a bone cement comprising:

a polymer component; and

a monomer component,

wherein, contacting the polymer component and the monomer component produces a mixture which attains a viscosity greater than 200 Pascal-second within 1 minute from onset of mixing and remains below 2000 Pascal-second until at least 6 minutes from onset of mixing.

Optionally, the polymer component comprises an acrylic polymer.

In an exemplary embodiment of the invention, there is provided a particulate mixture formulated for preparation of a bone cement, the mixture comprising:

Optionally, the polymer beads comprise a third subpopulation characterized by an MW of 10,000 Dalton to 15,000 Dalton.

In an exemplary embodiment of the invention, there is provided a method of making a polymeric bone cement, the method comprising:

In an exemplary embodiment of the invention, there is provided a cement kit, comprising:

(a) a liquid component including a monomer; and

(b) a powder component including polymeric beads,

characterized in that said powder component is provided in a substantially non-normal distribution of at least one of molecular weight of the polymeric beads and size of powder particles such that a cement mixed from the kit has both an increased immediate viscosity and an increased working window as compared to a cement having a substantially normal distribution.

Optionally, the substantially non-normal distribution is a skewed distribution.

Optionally, the substantially non-normal distribution comprises a relatively small component including higher molecular weight beads. Optionally, said component has an average molecular weight of at least a factor of 2 of an average molecular weight of said polymeric beads. Optionally, said factor is at least 3 or is at least 5.

Optionally, the substantially non-normal distribution comprises a relatively small component including smaller sized particles.

Exemplary non-limiting embodiments of the invention will be described with reference to the following description of embodiments in conjunction with the figures. Identical structures, elements or parts which appear in more than one figure are generally labeled with a same or similar number in all the figures in which they appear, in which:

FIG. 1 is a flow diagram illustrating an exemplary method 100 of preparation and behavior of exemplary cements according to the present invention;

FIG. 2 is a graph of viscosity profiles depicting viscosity (Pascal-second) as a function of time (minutes) for an exemplary cement according to the invention and an exemplary prior art cement;

FIGS. 3 and 4 are graphs indicating viscosity as Newtons of applied force per unit displacement (mm) under defined conditions for exemplary cements according to the invention and illustrate the time window for injection which is both early and long; and

FIG. 5 is a graph showing the results of bead size distribution analysis, for a bead formulation in accordance with an exemplary embodiment of the invention.

Overview of Preparation of Exemplary Bone Cement

FIG. 1 is a flow diagram illustrating preparation and behavior of exemplary cements according to some embodiments of the present invention.

In an exemplary embodiment of the invention, a liquid monomer and a powdered polymer component of a bone cement are combined 110. Optionally, liquid monomer is poured onto powdered polymer.

According to various embodiments of the invention, average polymer molecular weight and/or polymer molecular weight distribution and/or polymer bead size is precisely controlled in order to influence polymerization kinetics and/or cement viscosity. Alternatively or additionally, polymer and/or monomer components may contain ingredients which are not directly involved in the polymerization reaction.

In an exemplary embodiment of the invention, the polymer (e.g. an acrylic polymer such as PMMA) beads are divided into two or more sub-populations. Optionally, the sub populations are defined by molecular weight (MW). In an exemplary embodiment of the invention, the average molecular weight of the acrylic polymer in all the beads is in the range of about 300,000 to 400,000, optionally about 373,000 Dalton. This average MW for all beads was determined experimentally for a batch of beads which produced cement with a desired polymerization profile.

Optionally, the polymer beads are provided as part of an acrylic polymer mixture, for example a mixture including barium sulfate.

At 112 the components are mixed until the polymer is wetted by the monomer. Optionally, when wetting is 95 to 100% complete, the mixture has achieved a desired high viscosity, for example 500 Pascal-second or more. Optionally, mixing 112 is complete within 1, 5, 10, 15, 30, 60, 90, 120 or 180 seconds. In a modern medical facility, it can be advantageous to shorten the mixing time in order to reduce the demand on physical facilities and/or medical personnel. A savings of even 1 to 2 minutes with respect to previously available alternatives can be significant. In an exemplary embodiment of the invention, mixing 112 is conducted in a mixing apparatus of the type described in co-pending application U.S. Ser. No. 11/428,908, the disclosure of which is fully incorporate herein by reference.

After mixing 112 is complete, a working window 114 during which the cement remains viscous but has not fully hardened occurs. According to various exemplary embodiments of the invention, working window 114 may be about 2, 5, 8, 10, 15 or 20 minutes or intermediate or greater times. The duration of the working window may vary with the exact cement formulation and/or ambient conditions (e.g. temperature and/or humidity). Formulation considerations include, but are not limited to polymer MW (average and/or distribution), polymer bead size, concentrations of non-polymerizing ingredient and polymer:monomer ratio.

Working window 114, permits a medical practitioner sufficient time to load a high pressure injection device and inject 120 the cement into a desired location. Optionally, an injection needle or cannula is inserted into the body prior to, or concurrent with mixing 112 so that window 114 need only be long enough for loading and injection 120. Exemplary injection systems are disclosed in co-pending application U.S. Ser. No. 11/360,251 entitled “Methods, materials, and apparatus for treating bone and other tissue” filed Feb. 22, 2006, the disclosure of which is fully incorporated herein by reference.

In an exemplary embodiment of the invention, hardening 116 to a hardened condition occurs after working window 114. The cement hardens 116 even if it has not been injected.

Advantages with Respect to Relevant Medical Procedures

In an exemplary embodiment of the invention, cement with a viscosity profile as described above is useful in vertebral repair, for example in vertebroplasty and/or kyphoplasty procedures.

Optionally, use of cement which is viscous at the time of injection reduces the risk of material leakage and/or infiltrates into the intravertebral cancellous bone (interdigitaion) and/or reduces the fracture [see G Baroud et al, Injection biomechanics of bone cements used in vertebroplasty, Bio-Medical Materials and Engineering 00 (2004) 1-18]. Reduced leakage optionally contributes to increased likelihood of a positive clinical outcome.

In an exemplary embodiment of the invention, the viscosity of the bone cement is 500, optionally 1,000, optionally 1,500, optionally 2,000 Pascal-second or lesser or greater or intermediate values at the time injection begins, optionally 3, 2 or 1 minutes or lesser or intermediate times after mixing 112 begins. Optionally, the viscosity does not exceed 2,000 Pascal-second during working window 114. In an exemplary embodiment of the invention, this viscosity is achieved substantially as soon as 95-100% of the polymer beads are wetted by monomer.

Cement characterized by a high viscosity as described above may optionally be manually manipulated.

In an exemplary embodiment of the invention, cement is sufficiently viscous to move surrounding tissue as it is injected. Optionally, moving of the surrounding tissue contributes to fracture reduction and/or restoration of vertebral height.

An injected volume of cement may vary, depending upon the type and/or number of orthopedic procedures being performed. The volume injected may be, for example, 2-5 cc for a typical vertebral repair and as high as 8-12 cc or higher for repairs of other types of bones. Other volumes may be appropriate, depending for example, on the volume of space and the desired effect of the injection. In some cases, a large volume of viscous cement is loaded into a delivery device and several vertebrae are repaired in a single medical procedure. Optionally, one or more cannulae or needles are employed to perform multiple procedures.

Viscous cements according to exemplary embodiments of the invention may be delivered at a desired flow rate through standard orthopedic cannulae by applying sufficient pressure. Exemplary average injection rates may be in the range of 0.01 to 0.5 ml/sec, optionally about 0.05, about 0.075 or 0.1 ml/sec or lesser or intermediate or greater average flow rates. Optionally, the flow rate varies significantly during an injection period (e.g., pulse injections). Optionally, the flow rate is controlled manually or using electronic or mechanical circuitry. In an exemplary embodiment of the invention, medical personnel view the cement as it is being injected (e.g. via fluoroscopy) and adjust a flow rate and/or delivery volume based upon observed results. Optionally, the flow rate is adjusted and/or controlled to allow a medical practitioner to evaluate progress of the procedure based upon medical images (e.g. fluoroscopy) acquired during the procedure. In an exemplary embodiment of the invention, the cement is sufficiently viscous that advances into the body when pressure is applied above a threshold and ceases to advance when pressure is reduced below a threshold. Optionally, the threshold varies with one or more of cement viscosity, cannula diameter and cannula length.

Comparison of Exemplary Formulations According to Some Embodiments of the Invention to Previously Available Formulations

Although PMMA has been widely used in preparation of bone cement, previously available PMMA based cements were typically characterized by a persistent liquid state after mixing of components.

In sharp contrast, cements according to some exemplary embodiments of the invention are characterized by essentially no liquid state. Optionally, a direct transition from separate polymer and monomer components to a highly viscous state results from the presence of two or more sub-populations of polymer beads.

As a result of formulations based upon bead sub-populations, a viscosity profile of a cement according to an exemplary embodiment of the invention is significantly different from a viscosity profile of a previously available polymer based cement (e.g. PMMA) with a similar average molecular.

Because the viscosity profile of previously available PMMA cements is typically characterized by a rapid transition from high viscosity to fully hardened, these cements are typically injected into bone in a liquid phase so that they do not harden during injection.

In sharp contrast, exemplary cements according to the invention remain highly viscous during a long working window 114 before they harden. This long working window permits performance of a medical procedure of several minutes duration and imparts the advantages of the high viscosity material to the procedure.

It should be noted that while specific examples are described, it is often the case that the formulation will be varied to achieve particular desired mechanical properties. For example, different diagnoses may suggest different material viscosities which may, in turn lead to adjustment of one or more of MW (average and/or distribution), bead size and bead surface area.

In an exemplary embodiment of the invention, the cement is mixed 112 and reaches high viscosity outside the body. Optionally the materials are mixed under vacuum or ventilated. In this manner, some materials with potentially hazardous by-products can be safely mixed and then used in the body.

In an exemplary embodiment of the invention, the cement is formulated so that its mechanical properties match the bone in which it will be injected/implanted. In an exemplary embodiment of the invention, the cement is formulated to mechanically match healthy or osteoporotic trabecular (cancellous) bone. Optionally, the mechanical properties of the bone are measured during access, for example, based on a resistance to advance or using sensors provided through a cannula or by taking samples, or based on x-ray densitometry measurements. In an exemplary embodiment of the invention, strength of the cement varies as a function of one or more of a size of the high MW sub-population and/or a relationship between bead size and bead MW.

In general, PMMA is stronger and has a higher Young modulus than trabecular bone.

For example, healthy Trabecular bone can have a strength of between 1.5-8.0 mega Pascal and a Young modulus of 60-500 mega Pascal. Cortical bone, for example, has strength values of 65-160 mega Pascal and Young modulus of 12-40 giga Pascal. PMMA typically has values about half of Cortical bone (70-120 mega Pascal strength).

FIG. 2 is a plot of viscosity as a function of time for an exemplary bone cement according to the present invention. The figure is not drawn to scale and is provided to illustrate the principles of exemplary embodiments of the invention. The end of a mixing process is denoted as time 0. Mixing is deemed to end when 95-100% of acrylic polymer beads have been wetted with monomer. The graph illustrates an exemplary bone cement which enters a high viscosity plastic phase upon mixing so that it has substantially no liquid phase.

FIG. 2 illustrates that once a high viscosity is achieved, the viscosity remains relatively stable for 2, optionally 5, optionally 8 minutes or more. In an exemplary embodiment of the invention, this interval of stable viscosity provides a working window 114 (indicated here as Δt1) for performance of a medical procedure. In an exemplary embodiment of the invention, stable viscosity means that the viscosity of the cement changes by less than 200 Pascal-second during a window of at least 2 minutes optionally at least 4 minutes after mixing is complete. Optionally, the window begins 1, 2, 3, 4 or 5 minutes after mixing begins or lesser or intermediate times. In an exemplary embodiment of the invention, the viscosity of the cement remains below 1500, optionally 2000 Pascal-second for at least 4, optionally at least 6, optionally at least 8, optionally at least 10 minutes or intermediate or greater times from onset of mixing.

For purposes of comparison, the graph illustrates that an exemplary prior art cement reaches a viscosity comparable to that achieved by an exemplary cement according to the invention at time zero at a time of approximately 10.5 minutes post mixing and is completely set by about 15.5 minutes (Δt2).

A working window 114 during which viscosity is between 400 and 2000 Pascal-second for an exemplary cement according to some embodiments of the invention (Δt1) is both longer and earlier than a comparable window for an exemplary prior art cement (Δt2). Optionally, (Δt1) begins substantially as soon as mixing is complete.

Exemplary Cement Formulations

According to various exemplary embodiments of the invention, changes in the ratios between a powdered polymer component and a liquid monomer component can effect the duration of working window 114 and/or a viscosity of the cement during that window. Optionally, these ratios are adjusted to achieve desired results.

In an exemplary embodiment of the invention, the powdered polymer component contains PMMA (69.3% w/w); Barium sulfate (30.07% w/w) and Benzoyl peroxide (0.54% w/w).

In an exemplary embodiment of the invention, the liquid monomer component contains MMA (98.5% v/v); N, N-dimethyl-p-toluidine (DMPT) (1.5% v/v) and Hydroquinone (20 ppm).

In a first exemplary embodiment of the invention, 20±0.3 grams of polymer powder and 9±0.3 grams of liquid monomer are combined (weight ratio of ˜2.2:1).

In a second exemplary embodiment of the invention, 20±0.3 grams of polymer powder and 8±0.3 grams of liquid are combined (weight ratio of 2.5:1).

Under same weight ratio of second exemplary embodiment (2.5:1), a third exemplary embodiment may include a combination of 22.5±0.3 grams of polymer powder and 9±0.3 grams of liquid.

In general, increasing the weight ratio of polymer to monomer produces a cement which reaches a higher viscosity in less time. However, there is a limit beyond which there is not sufficient monomer to wet all of the polymer beads.

Optionally the powdered polymer component may vary in composition and contain PMMA (67-77%, optionally 67.5-71.5% w/w); Barium sulfate (25-35%; optionally 28-32% w/w) and Benzoyl peroxide (0.4-0.6% w/w) and still behave substantially as the powder component recipe set forth above.

Optionally the liquid monomer component may vary in composition and contain Hydroquinone (1-30 ppm; optionally 20-25 ppm) and still behave substantially as the liquid component recipe set forth above.

Viscosity Measurements Over Time for Exemplary Cements

In order to evaluate the viscosity profile of different exemplary batches of cement according to some embodiments of the invention, a bulk of pre-mixed bone cement is placed inside a Stainless Steel injector body. Krause et al. described a method for calculating viscosity in terms of applied force. (“The viscosity of acrylic bone cements”, Journal of Biomedical Materials Research, (1982): 16:219-243). This article is fully incorporated herein by reference.

In the experimental apparatus an inner diameter of the injector body is approximately 18 mm. A distal cylindrical outlet has an inner diameter of approximately 3 mm and a length of more than 4 mm. This configuration simulates a connection to standard bone cement delivery cannula/bone access needle. A piston applies force (F), thus causing the bone cement to flow through the outlet. The piston is set to move with constant velocity of approximately 3 mm/min. As a result, piston deflection is indicative of elapsed time.

The experimental procedure serves as a kind of capillary extrusion rheometer. The rheometer measures the pressure difference from an end to end of the capillary tube. The device is made of an 18 mm cylindrical reservoir and a piston. The distal end of the reservoir consist of 4 mm long 3 mm diameter hole. This procedure employs a small diameter needle and high pressure. Assuming steady flow, isothermal conditions and incompressibility of the tested material, the viscous force resisting the motion of the fluid in the capillary is equal to the applied force acting on the piston measured by a load cell and friction. Results are presented as force vs. displacement. As displacement rate was constant and set to 3 mm/min, the shear rate was constant as well. In order to measure the time elapses from test beginning, the displacement rate is divided by 3 (jog speed).

FIG. 3 indicates a viscosity profile of a first exemplary batch of cement according to the invention as force (Newtons) vs. displacement (mm). The cement used in this experiment included a liquid component and a powder component as described above in “Exemplary cement formulations”.

In this test (Average temperature: 22.3° C.; Relative Humidity: app. 48%) the cement was mixed for 30-60 seconds, then manipulated by hand and placed inside the injector. Force was applied via the piston approximately 150 seconds after end of mixing, and measurements of force and piston deflection were taken.

At a time of 2.5 minutes after mixing (0 mm deflection) the force applied was higher than 30 N.

At a time of 6.5 minutes after mixing (12 mm deflection) the force applied was about 150 N.

At a time of 7.5 minutes after mixing (15 mm deflection) the force applied was higher than 200 N.

At a time of 8.5 minutes after mixing (18 mm deflection) the force applied was higher than 500 N.

At a time of 9.17 minutes after mixing (20 mm deflection) the force applied was higher than 1300 N.

FIG. 4 indicates a viscosity profile of an additional exemplary batch of cement according to the invention as force (Newtons) vs. displacement (mm). The cement in this test was prepared according to the same formula described for the experiment of FIG. 3. In this test (Average 21.1° C.; Relative Humidity: app. 43%) the cement was mixed for approximately 45 seconds, then manipulated by hand and placed inside the injector. Force was applied via piston approximately 150 seconds after end of mixing, and measurements of force and piston deflection were taken.

At a time of 2.25 minutes after mixing (0 mm deflection) the force applied was higher than 30 N.

At a time of 8.25 minutes after mixing (18 mm deflection) the force applied was about 90 N.

At a time of 10.3 minutes after mixing (25 mm deflection) the force applied was higher than 150 N.

At a time of 11.4 minutes after mixing (28.5 mm deflection) the force applied was higher than 500 N.

At a time of 12.25 minutes after mixing (30 mm deflection) the force applied was higher than 800 N.

Results shown in FIGS. 3 and 4 and summarized hereinabove illustrate that exemplary bone cements according to some embodiments the invention achieve high viscosity in 2.25 minutes or less after mixing is completed. Alternatively or additionally, these cements are characterized by short mixing time (i.e. transition to highly viscous plastic phase in 30 to 60 seconds). The exemplary cements provide a “working window” for injection of 4.5 to 6.3 minutes, optionally longer if more pressure is applied and/or ambient temperatures are lower. These times correspond to delivery volumes of 14.9 and 20.8 ml respectively (vertebroplasty of a single vertebra typically requires about 5 ml of cement). These volumes are sufficient for most vertebral repair procedures. These results comply with the desired characteristics described in FIG. 2. Differences between the two experiments may reflect the influence of temperature and humidity on reaction kinetics.

Molecular Weight Distribution

In an exemplary embodiment of the invention, the average molecular weight (MW) is skewed by the presence of one or more small sub-population of beads with a molecular weight which is significantly different from a main sub-population of polymer beads. The one or more small sub-population of beads may have a MW which is significantly higher and/or significantly lower than the average MW.

In an exemplary embodiment of the invention, the presence of even a relatively small sub-population of polymer beads with a MW significantly above the average MW causes the cement to achieve a high viscosity in a short time after wetting of polymer beads with monomer solution. Optionally, increasing a size of the high MW sub-population increases the achieved viscosity. Alternatively or additionally, increasing an average MW of the high MW sub-population increases the achieved viscosity and/or decreases the time to reach high viscosity.

Optionally, the one or more small sub-population of beads are provided in a formulation in which, the average molecular weight of PMMA in all beads is 80,000, optionally 100,000, optionally 120,000, optionally 140,000, optionally 160,000, optionally 180,000, optionally, 250,000, optionally 325,000, optionally 375.000, optionally 400,000, optionally 500,000 Dalton or intermediate or lesser or greater values.

In another exemplary embodiment of the invention, the average molecular weight of the acrylic polymer in the beads is in the range of about 130,000 to 170,000, optionally about 160,000 Dalton.

In an exemplary embodiment of the invention, a main sub-population of PMMA beads has a MW of about 150,000 Dalton to about 500,000 Dalton, optionally about 250,000 Dalton to about 300,000 Dalton, optionally about 275,000 Dalton to about 280,000 Dalton. Optionally, about 90-98% [w/w], optionally about 93% to 98%, optionally about 95% to 97% of the beads belong to the main sub-population.

In an exemplary embodiment of the invention, a second high MW sub-population of PMMA beads has a MW of about 600,000 Dalton, to about 5,000,000 Dalton, optionally about 3,000,000 Dalton to about 4,000,000 Dalton, Optionally about 3,500,000 Dalton to about 3,900,000 Dalton. Optionally, approximately 0.25% to 5% [w/w], optionally about 1% to 4%, optionally about 2% to 3% of the beads belong to this high MW sub-population. Optionally, this high molecular weight sub-population comprises a styrene co-polymer. In an exemplary embodiment of the invention, a higher molecular weight in this sub-population of beads contributes to a high viscosity within 2, optionally within 1, optionally within 0.5 minutes or less of wetting of polymer beads with monomer solution.

In an exemplary embodiment of the invention, a third low MW sub-population of PMMA beads has a MW in the range of about 1,000 Dalton to about 75,000 Dalton, optionally about 10,000 Dalton to about 15,000 Dalton, optionally about 11,000 Dalton to about 13,000 Dalton. Optionally, approximately 0.5 to 2.0% [w/w], optionally about 1% of the beads belong to this sub-population.

Optionally the MW sub-populations are distinct from one another. This can cause gaps between sub-populations with respect to one or more parameters. In an exemplary embodiment of the invention, the sub-populations are represented as distinct peaks in a chromatographic separation process. Optionally, the peaks are separated by a return to baseline. Depending upon the sensitivity of detection, a background level of noise may be present. Optionally, gaps are measured relative to the noise level.

Optionally the sub-populations abut one another so that no gaps are apparent. In an exemplary embodiment of the invention, the sub-populations are represented as overlapping peaks in a chromatographic separation process. In this case, there is no return to baseline between the peaks.

Experimental Analysis of an Exemplary Batch of Cement

Sub-populations characterized by an average molecular weight were identified and quantitated using chromatographic techniques known in the art. Exemplary results described herein are based upon GPC analysis. Each peak in the GPC analysis is considered a sub-population. Similar analyses may be conducted using HPLC. Results are summarized in table 1.

TABLE I
MW distribution of polymer beads based upon GPC analysis of
a bone cement according to the powdered polymer component
described in “Exemplary cement formulations” hereinabove.
Fraction % of total PDI1 Mw2 Mn3
1 96.5 1.957 278,986 142,547
2 2.5 1.048 3,781,414 3,608,941
3 1.0 1.009 12,357 12,245
100.0 2.955 373,046 126,248
1polydispersity index (PDI), is a measure of the distribution of molecular weights in a given polymer sample and is equal to MW/Mn.
2MW is the weight average molecular weight in Daltons
3Mn is the number average molecular weight in Daltons

Table I illustrates an exemplary embodiment of the invention with three sub-populations of acrylic polymer beads.

The main sub-population (fraction 1) of PMMA beads has a molecular weight (MW) of 278,986 Dalton. About 96.5% of the beads belong to this sub-population.

A second sub-population (fraction 2) of PMMA beads has MW of 3,781,414 Dalton. Approximately 2.5% of the beads belong to this sub-population.

A third sub-population of PMMA beads (fraction 3) has an MW of 12,357 Dalton. Approximately 1% of the beads belong to this sub-population.

In an exemplary embodiment of the invention, cement comprising these three sub-populations is characterized by a short mixing time and/or achieves a viscosity of 500 to 900 Pascal-second in 0.5 to 3, optionally 0.5 to 1.5 minutes from the beginning of mixing and/or which remains below 2000 Pascal-second for at least 6 to 10 minutes after mixing. A short mixing time followed by a long working window is considered advantageous in orthopedic procedures where operating room availability and medical staff are at a premium.

Size Distribution

In an exemplary embodiment of the invention, the bone cement is characterized by beads with a size distribution including at least two sub-populations of polymer beads.

In an exemplary embodiment of the invention, polymer bead diameter is in the range of 10-250 microns, with a mean value of approximately 25, 30, 40, 50, 60 microns, or a lower or a higher or an intermediate diameter. In an exemplary embodiment of the invention, sub-populations of beads are defined by their size.

Optionally, a main sub-population of polymer (e.g. PMMA) beads is characterized by a diameter of about 20 to about 150, optionally about 25 to about 35, optionally an average of about 30 microns. Beads in this main sub-population are optionally far smaller than the smallest beads employed by Hernandez et al. (2005; as cited above). Presence of small beads can contribute to a rapid increase in viscosity after wetting with monomer.

Optionally a second sub-population of large polymer beads is characterized by a diameter of about 150 microns or more. Presence of large beads can slow down the polymerization reaction and prevent hardening, contributing to a long working window.

Optionally, the remaining beads are characterized by a very small average diameter, for example less than 20, optionally less than 15, optionally about 10 microns or less. Presence of very small beads can facilitate rapid wetting with monomer liquid during mixing and contribute to a fast transition to a viscous state with substantially no liquid phase.

Microscopic analysis indicates that the beads are typically spherical or spheroid.

Hernandez et al. (2005; as cited above) examined the possibility of adjusting the average polymer bead size by combining two types of beads with average sizes of 118.4μ (Colacry) and 69.7μ (Plexigum) together in different ratios. However, Hernandez's goal was a formulation which is “liquid enough to be injected”. All formulations described by Hernandez are characterized by an increase in viscosity from 500 Pascal-sec to 2000 Pascal-sec in about two minutes or less (corresponds to window 114). Hernandez does not hint or suggest that there is any necessity or advantage to increasing the size of this window.

Microscopic analysis also indicated that the barium sulfate particles are present as elongate amorphous masses with a length of approximately 1 micron. In some cases aggregates of up to 70 microns in size were observed. In some cases, barium sulfate particles and polymer beads aggregated together. Optionally, aggregates of Barium sulfate and polymer beads can delay wetting of polymer beads by monomer.

In an exemplary embodiment of the invention, MMA solvates and/or encapsulates the PMMA polymer beads and the viscosity of the initial mixture is high due to the solvation and/or friction between the beads. As the beads dissolve viscosity remains high due to polymerization which increases the average polymer MW.

The following table II shows an exemplary particle size distribution, for example, one suitable for the cement of Table I, based on an analysis of particles within the ranges of 0.375-2000 microns:

TABLE II
Particles size distribution of an exemplary powdered component
Vol. % 10 25 50 75 90
Max Beads 2.3 25.75 45.07 60.68 76.34
Diameter
[microns]

Experimental Analysis of a Second Exemplary Batch of Cement

Another example of a cement kit for mixture includes a liquid and a powder, which includes a mass of acrylic polymer beads. This cement kit is formulated as follows:

(a) liquid (9.2 gr)

(b) powder (20 gr)

As noted above, in other formulations the amounts may be varied, for example, to achieve specific mechanical (or other) properties, or they may be varied and achieve same mechanical properties. In another variation, medication may be added to the powder and/or liquid phases. Other liquid phases may be used as well, for example, as known in the art for PMMA-type cements. The ratios may be varied, for example, as described above.

Table III summarizes a molecular weight distribution of the acrylic bead component of this exemplary cement. It is hypothesized that providing a non-normal distribution of molecular weights with a heavier molecular weight component (e.g., by skewing the MW distribution by including relatively higher molecular weight beads) provides an increased immediate viscosity. In an exemplary embodiment of the invention, the higher MW beads are in a relatively small amount (for example, less than 20%, less than 10%, less than 5%) and have a MW of between 500,000 to 2,000,000 Dalton, optionally 600,000 to 1,200,000 Dalton (for example as shown in the table below).

TABLE III
MW distribution of polymer beads of a bone
cement of the second exemplary batch
Range of Molecular Weights [Dalton] % of total
1,000,000-2,000,000 0.38%
500,000-1,000,000 3.6%
250,000-500,000 12.4%
100,000-250,000 36.4%
 50,000-100,000 26.6%
25,000-50,000 14.2%
10,000-25,000 5.3%
 8,000-10,000 0.5%
5,000-8,000 0.4%

In an exemplary embodiment of the invention, the bone cement is characterized by beads with a size distribution including at least two sub-populations of different materials. Optionally, at least two sub-populations include polymer (e.g. PMMA) beads and Barium Sulfate particles. Optionally, the range of particles diameter of the Barium Sulfate is 0.01-15 microns, optionally 0.3 to 3 microns, optionally with an average of about 0.5 microns or lesser or intermediate or greater sizes.

In an exemplary embodiment of the invention, polymer bead diameter is in the range of 10-250 microns, optionally. 15-150 microns, with a mean value of approximately 25, 30, 40, 50, 60 microns. Lower or a higher or intermediate diameters are possible as well, for example, based on the setting considerations described above. In some cases, large particle sizes, for example, particles having diameters exceeding 120 microns (e.g., when the average diameter is on the order of 60 microns) are the result of Barium sulfate primary particle aggregation on PMMA particle beads.

An exemplary distribution of bead sizes for the exemplary cement of table III, based on an analysis of particles within the range of 0.04-2000 microns, is described in Table IV:

TABLE IV
Particles size distribution of a second exemplary
powdered component of bone cement
Vol. % 10 25 50 75 90
Max Beads 2 9 46.5 70.7 90.5
Diameter
[microns]

FIG. 5 is a graph which visually shows the values of table IV

Size and MW are Independent Variables

In an exemplary embodiment of the invention, size based and MW based sub-populations are determined independently. For example, MW may be determined chromatographically and size may be determined by microscopic analysis. As a result, beads classed in a single size sub-population may be classed in two or more MW sub-populations and/or beads classed in a single MW sub-population may be classed in two or more size sub-populations.

Mechanical Viscosity Increasing Agents

In an exemplary embodiment of the invention, the cement includes particles characterized by a large surface which do not participate in the polymerization reaction. The large surface area particles can impart added viscosity to the cement mixture independent of polymerization. Optionally, the added viscosity comes from friction of particles against one another in the cement.

Examples of materials which do not participate in the polymerization reaction but increase viscosity include, but are not limited to Zirconium, hardened acrylic polymer, barium sulfate and bone.

Optionally, materials which do not participate in the polymerization reaction but increase viscosity can at least partially substitute for high MW polymers in influencing a viscosity profile.

Desired Polymerization Reaction Kinetics

In an exemplary embodiment of the invention, mixture of polymer and monomer produces a high viscosity mixture with substantially no intervening liquid phase within 180, optionally within 120, optionally within 100, optionally within 60, optionally within 30, optionally within 15 seconds or greater or intermediate times from onset of mixing.

In an exemplary embodiment of the invention, once a high viscosity is achieved, the viscosity remains stable for 5 minutes, optionally 8 minutes, optionally 10 minutes or lesser or intermediate or greater times. Optionally, stable viscosity indicates a change of 10% or less in two minutes and/or a change of 20% or less in 8 minutes. The time during which viscosity is stable provides a working window for performance of a medical procedure.

These desired reaction kinetics can be achieved by adjusting one or more of average polymer MW, polymer MW distribution, polymer to monomer ratio and polymer bead size and/or size distribution.

General Considerations

In an exemplary embodiment of the invention, a powdered polymer component and a liquid monomer component are provided as a kit. Optionally, the kit includes instructions for use. Optionally, the instructions for use specify different proportions of powder and liquid for different desired polymerization reaction kinetics.

In an exemplary embodiment of the invention, a bone cement kit including at least two, optionally three or more separately packaged sub-populations of beads and a monomer liquid is provided. Optionally, the kit includes a table which provides formulations based on combinations of different amounts of bead sub-populations and monomer to achieve desired properties.

It is common practice in formulation of acrylic polymer cements to include an initiator (e.g. benzoyl peroxide; BPO) in the powdered polymer component and/or a chemical activator (e.g. DMPT) into the liquid monomer component. These components can optionally be added to formulations according to exemplary embodiments of the invention without detracting from the desired properties of the cement.

Optionally, an easily oxidized molecule (e.g. hydroquinone) is added to the liquid component to prevent spontaneous polymerization during storage (stabilizer). The hydroquinone can be oxidized during storage.

Optionally, cement may be rendered radio-opaque, for example by adding a radio-opaque material such as barium sulfate and/or zirconium compounds and/or bone (e.g. chips or powder) to the powder and/or liquid component.

While the above description has focused on the spine, other tissue can be treated as well, for example, compacted tibia plate and other bones with compression fractures and for fixation of implants, for example, hip implants or other bone implants that loosened, or during implantation. Optionally, for tightening an existing implant, a small hole is drilled to a location where there is a void in the bone and material is extruded into the void.

It should be noted that while use of the disclosed material as bone cement is described, non-bone tissue may optionally be treated. For example, cartilage or soft tissue in need of tightening may be injected with a high viscosity polymeric mixture. Optionally, the delivered material includes an encapsulated pharmaceutical and is used as a matrix to slowly release the pharmaceutical over time. Optionally, this is used as a means to provide anti-arthritis drugs to a joint, by forming a void and implanting an eluting material near the joint.

It should be noted that while use of PMMA has been described, a wide variety of materials can be suitable for use in formulating cements with viscosity characteristics as described above. Optionally, other polymers could be employed by considering polymer molecular weight (average and/or distribution) and/or bead size as described above. Optionally, at least some of the beads include styrene. In an exemplary embodiment of the invention, styrene is added to MMA beads in a volumetric ratio of 5-25%. Optionally, addition of styrene increases creep resistance.

According to various embodiments of the invention, a bone cement according to the invention is injected into a bone void as a preventive therapy and/or as a treatment for a fracture, deformity, deficiency or other abnormality. Optionally, the bone is a vertebral body and/or a long bone. In an exemplary embodiment of the invention, the cement is inserted into the medullary canal of a long bone. Optionally, the cement is molded into a rod prior to or during placement into the bone. In an exemplary embodiment of the invention, the rod serves as an intra-medular nail.

Exemplary Characterization Tools

Molecular weight and polydispersity can be analyzed, for example by Gel permeation chromatography(GPC) system (e.g. Waters 1515 isocratic HPLC pump with a Waters 2410 refractive-index detector and a Rheodyne (Coatati, Calif.) injection valve with a 20-μL loop (Waters Mass.)). Elution of samples with CHCl3 through a linear Ultrastyragel column (Waters; 500-Å pore size) at a flow rate of 1 ml/min provides satisfactory results.

It will be appreciated that various tradeoffs may be desirable, for example, between available injection force, viscosity, degree of resistance and forces that can be withstood (e.g. by bone or injection tools). In addition, a multiplicity of various features, both of method and of cement formulation have been described. It should be appreciated that different features may be combined in different ways. In particular, not all the features shown above in a particular embodiment are necessary in every similar exemplary embodiment of the invention. Further, combinations of the above features are also considered to be within the scope of some exemplary embodiments of the invention. In addition, some of the features of the invention described herein may be adapted for use with prior art devices, in accordance with other exemplary embodiments of the invention.

Section headers are provided only to assist in navigating the application and should not be construed as necessarily limiting the contents described in a certain section, to that section. Measurements are provided to serve only as exemplary measurements for particular cases, the exact measurements applied will vary depending on the application. When used in the following claims, the terms “comprises”, “comprising”, “includes”, “including” or the like means “including but not limited to”.

It will be appreciated by a person skilled in the art that the present invention is not limited by what has thus far been described. Rather, the scope of the present invention is limited only by the following claims.

Globerman, Oren, Beyar, Mordechay

Patent Priority Assignee Title
10039585, Jun 17 2003 DEPUY SYNTHES PRODUCTS, INC Methods, materials and apparatus for treating bone and other tissue
10111697, Sep 26 2003 DEPUY SYNTHES PRODUCTS, INC. Device for delivering viscous material
10272174, Sep 14 2006 DEPUY SYNTHES PRODUCTS, INC Bone cement and methods of use thereof
10485597, Mar 31 2003 DEPUY SYNTHES PRODUCTS, INC Remotely-activated vertebroplasty injection device
10494158, Oct 19 2006 DEPUY SYNTHES PRODUCTS, INC. Fluid delivery system
10631906, Nov 22 2005 DEPUY SYNTHES PRODUCTS, INC. Apparatus for transferring a viscous material
10799278, Mar 14 2003 DEPUY SYNTHES PRODUCTS, INC. Hydraulic device for the injection of bone cement in percutaneous vertebroplasty
9839460, Mar 31 2003 DEPUY SYNTHES PRODUCTS, INC Remotely-activated vertebroplasty injection device
9918767, Aug 01 2005 DEPUY SYNTHES PRODUCTS, INC Temperature control system
Patent Priority Assignee Title
1175530,
1612281,
1612996,
1733516,
1894274,
1929247,
2067458,
2123712,
2283915,
229932,
2394488,
2425867,
2435647,
2497762,
2521569,
2567960,
2745575,
2773500,
2808239,
2874877,
2918841,
2928574,
2970773,
3058413,
3063449,
3075746,
3108593,
3151847,
3198194,
3216616,
3224744,
3225760,
3254494,
3362793,
3381566,
3426364,
3515873,
3559956,
3568885,
3572556,
3605745,
3615240,
3674011,
3701350,
370335,
3750667,
3789727,
3796303,
3798982,
3846846,
3850158,
3867728,
3873008,
3875595,
3896504,
3901408,
3921858,
3931914, Jul 13 1973 Max Kabushiki Kaisha Powder ejector
3942407, May 30 1969 Expandable screw anchoring devices
3976060, Apr 09 1974 Messerschmitt-Bolkow-Blohm GmbH Extension apparatus, especially for osteotomic surgery
3993250, May 19 1975 Apparatus for spraying liquid materials
4011602, Oct 06 1975 Battelle Memorial Institute Porous expandable device for attachment to bone tissue
4062274, Jun 07 1976 Exhaust system for bone cement
4077494, Dec 15 1976 EPICOR INDUSTRIES, INC Grease gun
4079917, Jan 11 1974 Ronco Acquisition Corporation Whipper
408668,
4090640, Jul 24 1975 Hot melt adhesive pumping apparatus having pressure-sensitive feedback control
4093576, Apr 18 1975 Sulzer Brothers, Ltd. Mixture for anchoring bone implants
4105145, Sep 16 1976 ALTERNATIVE PACKAGING SOLUTIONS, L P Mechanically operated dispensing device
4115346, Feb 12 1974 KULZER GMBH Hydroxy group containing diesters of acrylic acids and their use in dental material
4146334, Sep 09 1977 Paint mixing and dispensing apparatus
4168787, Nov 18 1977 Superior, Inc. Variable stroke fluid lubricant dispenser
4170990, Jan 28 1977 Fried. Krupp Gesellschaft mit beschrankter Haftung Method for implanting and subsequently removing mechanical connecting elements from living tissue
4180070, Aug 29 1977 Abbott Laboratories Disposable double vial syringe
4185072, Feb 17 1977 Diemolding Corporation Orthopedic cement mixer
4189065, Feb 04 1976 ESPE STIFTUNG & CO PRODUKTIONS- UND VERTRIEBS KG Metering dispenser for high-viscosity compositions
4198383, Aug 21 1978 Apparatus for continuous preparation of acrylonitrilebutadienstyrene copolymer
4198975, Oct 06 1978 Self-injecting hypodermic syringe device
4204531, Dec 28 1977 Intramedullary nail with expanding mechanism
4239113, Jun 02 1977 KULZER GMBH Composition for the preparation of bone cement
4250887, Apr 18 1979 Dardik Surgical Associates, P.A. Remote manual injecting apparatus
4257540, Oct 26 1978 McNeil Corporation Hand-held battery-powered grease gun
4268639, Oct 02 1978 NATEC, INSTITUT FUR NATURWISSENSCHAFTLICHTECHNISCHE DIENSTE GMBH Self-curing composition based upon polymethylmethacrylate and process for manufacturing said self-curing composition
4274163, Jul 16 1979 The Regents of the University of California Prosthetic fixation technique
4276878, Aug 20 1979 Injection syringe
4277184, Aug 14 1979 Disposable orthopedic implement and method
4298144, Apr 12 1978 Jakob Pressl, Sohne Grease gun
4309777, Nov 13 1980 Artificial intervertebral disc
4312343, Jul 30 1979 LEVEEN, ROBERT F , Syringe
4313434, Oct 17 1980 Fracture fixation
4326567, Dec 26 1979 Packaging Resources Incorporated; UNION BANK OF SWITZERLAND, NEW YORK BRANCH, AS AGENT Variable volume, positive displacement sanitary liquid dispensing machine
4338925, Dec 20 1979 Pressure injection of bone cement apparatus and method
4341691, Feb 20 1980 Zimmer, Inc. Low viscosity bone cement
4346708, Apr 20 1981 DEVICE DEVELOPMENTS, INC Syringe
4349921, Jun 16 1980 Intervertebral disc prosthesis
4359049, Apr 02 1980 Immuno Aktiengesellschaft fur Chemisch-Medizinische Produkte Apparatus for applying a tissue adhesive on the basis of human or animal proteins
4373217, Feb 16 1979 Merck Patent Gesellschaft mit beschrankter Haftung Implantation materials and a process for the production thereof
4380398, Sep 16 1980 BABURCO INC , A CORP OF CANADA Dispersion mixer
4400170, Sep 29 1981 American Home Products Corporation Implanting device and implant magazine
4403989, Sep 14 1981 American Home Products Corporation Injection device
4404327, Oct 31 1979 Orthopaedic cement from acrylate polymers
4405249, Mar 28 1980 National Research Development Corporation Dispensing apparatus and method
4409966, May 29 1981 UNITED STATES OF AMERICA, AS REPRESENTED BY THE UNITED STATES DEPARTMENT OF ENERGY Method and apparatus for injecting a substance into the bloodstream of a subject
4453539, Mar 01 1982 The University of Toledo Expandable intramedullary nail for the fixation of bone fractures
4474572, Sep 29 1981 American Home Products Corporation Implanting device and implant magazine
4475856, Dec 21 1979 Telefonaktiebolaget L M Ericsson Expansion screw with an expansion sleeve having an outer cylindrical surface and regions of greater and lesser wall thickness
4476866, Aug 06 1982 Thomas J., Fogarty Combined large and small bore syringe
4487602, Sep 14 1981 American Home Products Corporation Injection device
4494535, Jun 24 1981 Hip nail
4500658, Jun 06 1983 AUSTENAL, INC Radiopaque acrylic resin
4503169, Apr 19 1984 Minnesota Mining and Manufacturing Company; MINNESOTA MINING AND MANUFACTURING COMPANY, A CORP OF DE Radiopaque, low visual opacity dental composites containing non-vitreous microparticles
4522200, Jun 10 1983 ACE Orthopedic Company Adjustable intramedullar rod
4543966, Jun 10 1981 SIMS SURGICAL EQUIPMENT LIMITED Biopsy needle
4546767, Oct 27 1983 Cement injection device
4554914, Oct 04 1983 Prosthetic vertebral body
4558693, Aug 29 1983 Penile implant
4562598, Apr 01 1982 KRANZ, CURT Joint prosthesis
4576152, Oct 21 1982 SULZER BROTHERS LIMITED A CORP OF SWITZERLAND Injector for bone cement
4588583, Dec 11 1982 PAGANELLA INTERNATIONAL N V Surgical material
4593685, Oct 17 1983 Stryker Technologies Corporation Bone cement applicator
4595006, Aug 16 1982 Apparatus for cemented implantation of prostheses
4600118, Feb 02 1984 New Rule Products, Inc Ferrule dispenser
4605011, Mar 23 1983 Ascendia AB Cell sampling apparatus
4632101, Jan 31 1985 Orthopedic fastener
4636217, Apr 23 1985 Regents of The University of Minnesota Anterior spinal implant
4642099, Jul 31 1984 N J PHILLIPS PTY LIMITED, 24-26 MIDDLETON ROAD, DEE WHY, NEW SOUTH WALES, 2099, AUSTRALIA, A CORP OF AUSTRALIA Injector
4650469, Oct 19 1984 SMITHS MEDICAL MD, INC Drug delivery system
4651904, Dec 02 1983 BRAMLAGE GESELLSCHAFT MIT BESCHRANKTER HAFTUNG, KUSTERMEYERSTRASSE 31, 2842 LOHNE OLDENBURG, GERMANY, A CORP OF GERMANY Dispenser for pasty compositions, particularly toothpaste dispenser
4653487, Jan 29 1986 Intramedullary rod assembly for cement injection system
4653489, Apr 02 1984 Fenestrated hip screw and method of augmented fixation
4664298, May 01 1985 STEWART-WARNER ALEMITE LICENSCO INC Dual mode grease gun
4664655, Mar 20 1986 Norman, Orentreich High viscosity fluid delivery system
4668220, Oct 26 1984 Infors GmbH Infusion pump
4668295, Apr 25 1985 University of Dayton Surgical cements
4670008, Jul 01 1985 High flux threaded needle
4671263, Jul 11 1984 THURGAUER KANTONALBANK, A CORPORATION CHARTERED IN AND EXISTING UNDER THE LAWS OF SWITZERLAND, THAT MAINTAINS ITS PRINCIPAL OFFICES AT: Device and process for mixing and applying bone cement
4676655, Nov 18 1985 Plunger type cartridge mixer for fluent materials
4676781, Dec 31 1982 N.J. Phillips Pty. Limited Injector
4686973, Oct 12 1984 Dow Corning Corporation Method of making an intramedullary bone plug and bone plug made thereby
4697584, Oct 12 1984 HAYNES, DARREL W Device and method for plugging an intramedullary bone canal
4697929, Oct 28 1986 Charles Ross & Son Company Planetary mixers
4704035, Oct 06 1986 B&P PROCESS EQUIPMENT AND SYSTEMS L L C Remotely transmitting batch mixer
4710179, Oct 27 1986 Habley Medical Technology Corporation Snap-on vernier syringe
4714721, Jun 07 1984 Ernst Leitz Wetzlar GmbH Composite plastics-based material for prosthesis purposes
4717383, Jul 31 1984 N J PHILLIPS PTY LIMITED Injector
4718910, Jul 16 1985 Bone cement and process for preparing the same
4722948, Mar 16 1984 HOLOMETRIX, INC Bone replacement and repair putty material from unsaturated polyester resin and vinyl pyrrolidone
4735616, Jun 20 1985 Immuno Aktiengesellschaft fur Chemisch-Medizinische Produkte Arrangement for applying a tissue adhesive
4737151, Jul 25 1986 Syringe injector
4747832, Sep 02 1983 Device for the injection of fluid, suitable for implantation
4758096, Dec 23 1985 SCANDIMED INTERNATIONAL AB FORMERLY MIT AB Apparatus for mixing bone cement in vacuum
4758234, Mar 20 1986 Norman, Orentreich High viscosity fluid delivery system
4759769, Feb 12 1987 Health & Research Services Inc. Artificial spinal disc
4762515, Jan 06 1987 IVY ANIMAL HEALTH, INC Medicament implant applicator
4767033, Jul 31 1986 S C JOHNSON & SON, INC Manually operated gear pump spray head
4772287, Aug 20 1987 RAYMEDICA, LLC Prosthetic disc and method of implanting
4782118, Jun 20 1985 Societe Anonyme dite: CERAVER Cement for fixing a bone prosthesis
4786184, Feb 04 1987 Institut Problem Mekhainiki Apparatus for mixing heterogeneous substances
4791150, Oct 01 1985 Bonar Cole Polymers Limited; The London Hospital Medical College Composition for use in making bone cement
4792577, Jul 16 1987 Johnson & Johnson Dental Products Company Stain-resistant no-mix orthodontic adhesive
4804023, May 23 1986 Avdel Limited, British Company Hydraulic fluid replenishment device
4813870, Mar 09 1987 Minnesota Mining and Manufacturing Company; MINNESOTA MINING & MANUFACTURING COMPANY, SAINT PAUL, MN A CORP OF DE Dispenser for viscous liquids
4815454, Nov 16 1987 DOZIER, PATRICIA S , AS HER SOLE AND SEPARATE PROPERTY Apparatus and method for injecting bone cement
4815632, May 04 1985 Jencons (Scientific) Limited Liquid dosing device with digital display
4826053, Jul 07 1986 Mixpac Systems AG Dispenser for cartridges
4830227, Nov 10 1986 Metal Box plc Dispensers for pasty or viscous products
4837279, Feb 22 1988 Howmedica Osteonics Corp Bone cement
4854312, Apr 13 1988 The University of Toledo Expanding intramedullary nail
4854482, Feb 23 1987 Hilti Aktiengesellschaft Dispensing device for flowable masses
4854716, May 14 1987 ALLO PRO AG, A CORP OF SWITZERLAND Device for processing bone cement
4863072, Aug 18 1987 Single hand operable dental composite package
4869906, Apr 18 1986 Merck Patent Gesellschaft mit beschrankter Haftung Tricalcium phosphate for implant materials wherein the pores of the tricalciumphosphate are filled with antibiotic and amino acid
4872936, Oct 09 1985 ERNST MUHLBAUER GMBH & CO KG Polymerizable cement mixtures
4892231, Jul 16 1986 Metal Box p.l.c. Pump chamber dispenser
4892550, Dec 30 1985 Endoprosthesis device and method
4902649, Sep 10 1986 Showa Denko Kabushiki Kaisha Hard tissue substitute composition
4904260, Aug 20 1987 RAYMEDICA, LLC Prosthetic disc containing therapeutic material
4908017, May 14 1985 MEDEX, INC Failsafe apparatus and method for effecting syringe drive
4910259, Sep 26 1988 WOLFF & KAABER A S, 50% A CORP OF DENMARK; JENSEN, JORGEN STEEN, 50% Bone cement
4927866, Feb 29 1988 ESPE Stiftung & Co. Produktions- und Vertriebs KG Shapable material and shaped articles obtainable therefrom
4932969, Jan 08 1987 Zimmer GmbH Joint endoprosthesis
4935029, Jun 22 1987 Matsutani Seisakusho Co., Ltd. Surgical needle
4944065, Sep 27 1988 NILFISK-ADVANCE A S Suction cleaner
4944726, Nov 03 1988 APPLIED VASCULAR DEVICES, A CORP OF CA Device for power injection of fluids
4946077, Mar 11 1988 In-line air-bleed valve for hand-operated grease guns
4946285, Mar 08 1990 PREMARK FEG L L C Bowl scraper attachment for planetary food mixer
4946901, Dec 10 1986 ESPE Dental AG; 3M ESPE AG Polymerizable compositions, process for the preparation thereof, and use thereof as dental compositions
4961647, Apr 04 1986 Stryker Corporation Orthopedic cement mixer
4966601, Mar 21 1986 THURGAUER KANTONALBANK, A CORPORATION CHARTERED IN AND EXISTING UNDER THE LAWS OF SWITZERLAND, THAT MAINTAINS ITS PRINCIPAL OFFICES AT: Evacuatable bone cement syringe
4968303, Sep 27 1988 Eli Lilly and Company Hypodermic syringe holder
4969888, Feb 09 1989 Kyphon SARL Surgical protocol for fixation of osteoporotic bone using inflatable device
4973168, Jan 13 1989 ZIMMER TECHNOLOGY, INC Vacuum mixing/bone cement cartridge and kit
4973301, Jul 11 1989 Catheter and method of using same
4973334, Jan 16 1987 Allo Pro AG Device for ejecting or taking in liquid or paste-like media
4978336, Sep 29 1987 Baxter International Inc; BAXTER HEALTCHARE SA Biological syringe system
4983164, Apr 14 1987 Astra Tech Aktiebolag Automatic two-chamber injector
4994065, May 18 1990 ZIMMER TECHNOLOGY, INC Apparatus for dispensing low viscosity semi-fluid material under pressure
4995868, Oct 12 1988 Bard Limited Catheter
5004501, Jun 01 1988 TECRES SpA Two phase cement mixture, particularly suitable for othopaedics
5006112, Nov 12 1988 MTS SCHWEINFURT GMBH, A FRESENIUS CORP Syringe pump
5012066, Aug 31 1989 Matsutani Seisakusho Co., Ltd. Method of and apparatus for manufacturing eyeless suture needle
5015233, Apr 17 1989 FREEDOM MACHINE, INC Pneumatic inflation device
5018919, Apr 15 1989 Bergwerksverband GmbH Combined rigid profile and stretching roof bolt with expansion element
5022563, Jan 10 1990 ELECTRON FUSION DEVICES, INC Dispenser-gun assembly for viscous fluids and dispenser therefor
5024232, Oct 07 1986 The Research Foundation of State University of NY Novel radiopaque heavy metal polymer complexes, compositions of matter and articles prepared therefrom
5028141, Jul 22 1988 Ika-Maschinenbau Janke & Kunkel GmbH & Co. KG. Mixing machine
5037473, Nov 18 1987 Denture liners
5049157, Jun 29 1978 Osteo AG Reinforced bone cement
5051482, Nov 19 1986 AO-Forschungsinstitut Davos Method and apparatus for preparing a self-curing two-component powder liquid bone cement
5059193, Nov 20 1989 ZIMMER SPINE, INC Expandable spinal implant and surgical method
5059199, Apr 12 1989 Olympus Optical Co., Ltd. Treating device for endoscopes
5061128, Jan 16 1989 MASCHINENFABRIK LORENZ AG, A CORP OF GERMANY Mechanism for the drive of a tool spindle
5071040, Mar 09 1990 Howmedica Osteonics Corp Surgical adhesives mixing and dispensing implement
5074871, Dec 07 1989 EVI Corporation Catheter atherotome
5078919, Mar 20 1990 UNITED STATES OF AMERICA, THE, AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF ENERGY Composition containing aerogel substrate loaded with tritium
5092888, May 19 1989 Tokuyama Soda Kabushiki Kaisha Hardening material
5102413, Nov 14 1990 Inflatable bone fixation device
5108403, Nov 09 1990 Bone waxing device
5108404, Feb 09 1989 Kyphon SARL Surgical protocol for fixation of bone using inflatable device
5112333, Feb 07 1990 Intramedullary nail
5114240, May 12 1989 WOLFF & KAABER A S, RUGMARKEN 28, DK-3520 FARUM A DANISH LIMITED COMPANY Method and a device for preparing a mixture of a solid and a liquid component
5116335, Sep 18 1989 Intramedullary hybrid nail and instrumentation for installation and removal
5122400, Nov 20 1987 Stewkie Limited Inflatable articles and method of creating inflatable products
5123926, Feb 22 1991 Perumala Corporation Artificial spinal prosthesis
5125971, Jun 30 1989 TDK Corporation Living hard tissue replacement, its preparation
5131382, Mar 27 1989 KARL STORZ-ENDOSCOPY-AMERICA, INC CALIFORNIA CORPORATION Endoscopic percutaneous discectomy device
5141496, Nov 03 1988 Spring impelled syringe guide with skin penetration depth adjustment
5145250, Jun 15 1989 Merck Patent Gesellschaft MIT Beschraenkter Haftung Process for the preparation of bone cement
5147903, Jun 16 1988 HERAEUS KULZER GMBH & CO KG Dental materials
5171248, Feb 27 1991 ZIMMER, INC Medullary caliper
5171278, Feb 22 1991 Perumala Corporation Middle expandable intervertebral disk implants
5181918, Aug 10 1990 THERA Patent GmbH & Co. KG Gesellschaft Fuer industrielle Schutzrechte Granules syringe
5188259, Feb 01 1991 Caulking gun with belt worn cartridge
5190191, Mar 13 1991 Apparatus for measured and unmeasured dispensing of viscous fluids
5192327, Mar 22 1991 DEPUY ACROMED, INC Surgical prosthetic implant for vertebrae
5193907, Dec 04 1990 TECRES SpA Process and apparatus for the mixing and direct emplacement of a two-component bone cement
5209753, Nov 03 1989 Bone screw
5217147, Mar 09 1992 KAUFMAN PRODUCTS INC Liquid dispenser with compression chamber
5219897, Feb 10 1992 Dental and orthopedic cement method and preforms
5236445, Apr 05 1991 Smith & Nephew, Inc Expandable bone anchor and method of anchoring a suture to a bone
5242983, Mar 19 1992 Edison Polymer Innovation Corporation Polyisobutylene toughened poly(methyl methacrylate)
5252301, Jan 11 1990 Cemvac System AB Apparatus for the preparation of bone cement
5254092, Sep 15 1992 AMS Research Corporation Fluid flow check valve
5258420, Jul 30 1987 Howmedica Osteonics Corp Bone cement for sustained release of substances
5264215, Oct 19 1989 Mitsui Chemicals, Inc Bone cement composition, cured product thereof, implant material and process for the preparation of the same
5268001, Sep 25 1990 INNOVASIVE DEVICES, INC Bone fastener
5269762, Apr 21 1992 GE Healthcare AS Portable hand-held power assister device
5275214, Oct 28 1992 Apparatus for unloading pressurized fluid
5276070, Jan 25 1990 Howmedica Osteonics Corp Bone cement
5277339, Mar 26 1992 Alemite, LLC Dual mode pistol-grip grease gun
5279555, Aug 24 1992 Merck & Co., Inc.; MERCK & CO , INC Device for injecting implants
5290260, May 31 1991 Cook Medical Technologies LLC Rotational pressure drive for a medical syringe
5295980, Oct 30 1989 Multi-use cannula system
5302020, Apr 15 1992 Georg Fischer AG Planetary mixing apparatus
5303718, Jan 15 1992 Method and device for the osteosynthesis of bones
5304147, Aug 27 1991 Johnson Medical Development Corp. Injection syringe
5318532, Oct 03 1989 C. R. Bard, Inc. Multilumen catheter with variable cross-section lumens
5328262, Feb 07 1992 SCANDIMED INTERNATIONAL AB FORMERLY MIT AB Method for producing reduced porosity bone cement
5328362, Mar 11 1992 Soft resilient interocclusal dental appliance, method of forming same and composition for same
5331972, Dec 03 1992 Carefusion 2200, Inc; CARDINAL HEALTH CMP 200, INC Bone marrow biopsy, aspiration and transplant needles
5333951, Jul 22 1992 Toyo Sekkei Co., Ltd. Roll mixing machine and method
5334184, Jun 30 1992 Apparatus for intramedullary fixation broken bones
5334626, Jul 28 1992 ZIMMER TECHNOLOGY, INC Bone cement composition and method of manufacture
5336699, Feb 20 1992 Orthopaedic Research Institute Bone cement having chemically joined reinforcing fillers
5336700, Feb 10 1992 Dental and orthopedic cement methods and preforms
5344232, Sep 30 1991 Stryker Corporation Bone cement mixing and loading apparatus
5348391, Nov 16 1993 Manual bone cement mixing method
5348548, Jan 08 1990 BECTON DICKINSON FRANCE S A Two-compartment storage and transfer flask
5350372, May 19 1992 Nissho Corporation Solvent container with a connecter for communicating with a drug vial
5354287, Jan 16 1991 RANBAXY PHARMACEUTICALS, INC Injector for delivering fluid to internal target tissue
5356382, Oct 23 1992 APPLIED MEDICAL RESEARCH, INC Percutaneous tract measuring and forming device
5368046, Sep 09 1992 Covidien AG Bone marrow needle assembly
5368386, Nov 16 1993 Manual bone cement mixing device
5370221, Jan 29 1993 BIOMER C V Flexible package for bone cement components
5372583, Nov 25 1992 CARDIOPULMONARY SPECIALITES, INC Bone marrow infuser and method of use
5374427, Jun 20 1990 Thera Patent GmbH & Co. KG Implantable active substance depot material
5376123, Aug 07 1991 AO-Forschungsinstitut Davos Adaptable stem for endoprosthesis
5380772, Dec 11 1989 G-C Toshi Kogyo Corporation Modelling liquid for dental porcelain
5385081, Sep 09 1993 ARDE INC Fluid storage tank employing a shear seal
5385566, Feb 20 1992 Device and a method for use in transplantation of bone tissue material
5387191, Feb 06 1989 Board of Regents of the Univ. of Okla. Flushing needle
5390683, Feb 22 1991 Perumala Corporation Spinal implantation methods utilizing a middle expandable implant
5395167, Nov 16 1993 Manual bone cement mixing system
5395326, Oct 20 1993 Habley Medical Technology Corporation Pharmaceutical storage and mixing syringe having high pressure assisted discharge
5398483, Jan 29 1993 BIOMER C V Method and apparatus for packaging, mixing and delivering bone cement
5401806, Jan 04 1991 The Secretary of State for Health in Her Britannic Majesty's Government Biocompatible mouldable polymeric material
5407266, Jun 07 1991 List AG Mixing kneader with rotating shafts and kneading bars
5411180, May 07 1993 MMP ACQUISITION CORP Self-contained hydraulic dispensing mechanism with pressure relief regulator
5415474, Sep 30 1991 Stryker Corporation Bone cement mixing and loading apparatus
5423824, Mar 23 1992 Aprio Medical AB Method of accessing hard tissue
5423850, Oct 01 1993 Medtronic Spine LLC Balloon compressor for internal fixation of bone fractures
5431654, Sep 30 1991 Stryker Corporation Bone cement injector
5435645, Dec 29 1989 TECRES SpA Process and apparatus for the mixing and direct emplacement of a two-component bone cement
5441502, Feb 17 1993 MITEK SURGICAL PRODUCTS, INC System and method for re-attaching soft tissue to bone
5443182, Jun 11 1993 Howmedica Osteonics Corp Methods and apparatus for preparing and delivering bone cement
5445639, May 10 1989 ZIMMER SPINE, INC Intervertebral reamer construction
5450924, Jan 05 1995 CHUAN JIING ENTERPRISES CO , LTD Portable oil suction device
5454365, Nov 05 1990 BONUTTI 2003 TRUST-A, THE Mechanically expandable arthroscopic retractors
5456267, Mar 18 1994 Bone marrow harvesting systems and methods and bone biopsy systems and methods
5468245, Feb 03 1994 Biomedical cement bonding enhancer
5480400, Oct 01 1993 Medtronic Spine LLC Method and device for internal fixation of bone fractures
5480403, Mar 22 1991 United States Surgical Corporation Suture anchoring device and method
5482187, Sep 13 1993 Hygienix, Inc. Dispenser for viscous substances
5492247, Jun 02 1994 Automatic soap dispenser
5494349, Dec 06 1991 Summit Medical Limited Bone cement mixing device
5501374, Jun 17 1994 VITAL PRODUCTS, CO Device for extruding high viscosity fluid having multiple modes of operation
5501520, Feb 07 1992 SCANDIMED INTERNATIONAL AB FORMERLY MIT AB Device for producing reduced porosity bone cement
5501695, May 27 1992 ANSPACH EFFORT, INC , THE Fastener for attaching objects to bones
5512610, Jul 28 1992 ZIMMER TECHNOLOGY, INC Bone cement composition
5514135, Jul 06 1993 Bone cement delivery gun
5514137, Dec 06 1993 Fixation of orthopedic devices
5518498, Oct 09 1992 Angiomed AG Stent set
5520690, Apr 13 1995 Warsaw Orthopedic, Inc Anterior spinal polyaxial locking screw plate assembly
5522816, Mar 09 1994 DEPUY ACROMED, INC Transverse connection for spinal column corrective devices
5522899, Jun 28 1988 Warsaw Orthopedic, Inc Artificial spinal fusion implants
5526853, Aug 17 1994 B BRAUN MEDICAL, INC PA CORPORATION Pressure-activated medication transfer system
5531519, Jul 06 1993 Automated bone cement mixing apparatus
5531683, Aug 13 1992 PESCADERO BEACH HOLDINGS CORPORATION Mixing and delivery syringe assembly
5534028, Apr 20 1993 Howmedica Osteonics Corp Hydrogel intervertebral disc nucleus with diminished lateral bulging
5536262, Sep 07 1994 Cedars-Sinai Medical Center Medical coupling device
5545460, Jun 11 1993 Howmedica Osteonics Corp Methods and apparatus for preparing and delivering bone cement
5548001, Feb 15 1990 Heraeus Kulzer GmbH & Co. KG Swellable bead polymer containing fillers
5549380, Mar 21 1994 Biomet Cementing Technologies AB Mixing device for manufacturing bone cement
5549381, May 19 1995 SMITH & NEPHEW RICHARDS INC Method and apparatus for mixing polymeric bone cement components
5549679, May 20 1994 SPINEOLOGY, INC Expandable fabric implant for stabilizing the spinal motion segment
5551778, Jul 16 1994 Biomet Deutschland GmbH A cylinder for mixing components to form bone cement
5554101, Aug 05 1991 United States Surgical Corporation Surgical retractor
5556201, Jul 21 1995 Middleby Marshall Inc. Bowl scraper for commercial or industrial size food mixers
5558136, Jan 31 1994 Stryker Corporation Bone cement cartridge with secondary piston
5558639, Jun 10 1993 Ambulatory patient infusion apparatus
5571189, May 20 1994 SPINEOLOGY, INC Expandable fabric implant for stabilizing the spinal motion segment
5573265, Nov 05 1993 Fichtel & Sachs AG Stabilizer system for a motor vehicle suspension system with a rotary actuator
5578035, May 16 1995 Expandable bone marrow cavity fixation device
5586821, Oct 10 1995 ZIMMER TECHNOLOGY, INC Bone cement preparation kit
5588745, Sep 02 1994 Howmedica Osteonics Corp Methods and apparatus for mixing bone cement components using an evacuated mixing chamber
5591197, Mar 14 1995 Advanced Cardiovascular Systems, INC Expandable stent forming projecting barbs and method for deploying
5601557, May 20 1982 Anchoring and manipulating tissue
5603701, Mar 27 1995 Ultradent Products, Inc. Syringe apparatus with threaded plunger for delivering tooth composites and other solid yet pliable materials
5609637, Jul 09 1993 Space keeper, in particular for an intervertebral disk
5624184, Oct 10 1995 ZIMMER TECHNOLOGY, INC Bone cement preparation kit having a breakable mixing shaft forming an output port
5630806, Aug 13 1991 Hudson International Conductors Spiral wrapped medical tubing
5634880, May 22 1995 JOHNSON & JOHNSON MEDICAL, INC Endoscope pressure equalization system and method
5637097, Apr 15 1992 Penetrating instrument having an expandable anchoring portion
5638997, Sep 18 1995 ZIMMER TECHNOLOGY, INC Bone cement injector gun
5641010, Jul 14 1994 International Medication Systems, Limited Mixing and dispensing apparatus
5645598, Jan 16 1996 Howmedica Osteonics Corp Spinal fusion device with porous material
5647856, Sep 23 1993 HERAEUS KULZER GMBH & CO KG Syringe for the controlled discharge of viscous materials
5653686, Jan 13 1995 COULTER INTERNATIONAL CORP Closed vial transfer method and system
5658310, Oct 01 1993 Medtronic Spine LLC Balloon compressor for internal fixation of bone fractures
5660186, Jun 07 1995 Marshfield Clinic Spiral biopsy stylet
5665067, Feb 28 1994 Baxalta Innovations GmbH Apparatus for applying a multiple-component tissue adhesive
5681317, Jun 12 1996 DePuy Orthopaedics, Inc Cement delivery system and method
5683451, Jun 08 1994 Medtronic Ave, Inc Apparatus and methods for deployment release of intraluminal prostheses
5685826, Nov 05 1990 General Surgical Innovations, Inc Mechanically expandable arthroscopic retractors and method of using the same
5690606, Jun 20 1994 Tisssue spreading surgical instrument
5693100, Feb 22 1991 Middle expandable intervertebral disk implant
5697977, Mar 18 1994 Method and apparatus for spondylolisthesis reduction
5698611, Mar 13 1995 GC Corporation Denture base relining resins
5702448, Sep 17 1990 Prosthesis with biologically inert wear resistant surface
5704895, Dec 28 1979 WPAMS ACQUISITION CORP Implantable penile prosthetic cylinder with inclusive fluid reservoir
5707390, Mar 02 1990 General Surgical Innovations, Inc Arthroscopic retractors
5718707, Jan 22 1997 Method and apparatus for positioning and compacting bone graft
5720753, Mar 22 1991 United States Surgical Corporation Orthopedic fastener
5725341, Jan 08 1997 Self fusing fastener
5725529, Sep 24 1990 Innovasive Devices, Inc. Bone fastener
5747553, Apr 26 1995 Reinforced Polymer Inc.; REINFORCED POLYMER, INC Low pressure acrylic molding composition with fiber reinforcement
5752935, Mar 08 1988 Boston Scientific Scimed, Inc Balloon catheter inflation device
5752969, Jun 17 1993 Sofamor S.N.C. Instrument for the surgical treatment of an intervertebral disc by the anterior route
5752974, Dec 18 1995 ANGIOTECH PHARMACEUTICALS, INC Injectable or implantable biomaterials for filling or blocking lumens and voids of the body
5755732, Mar 16 1994 United States Surgical Corporation Surgical instruments useful for endoscopic spinal procedures
5759186, Jun 14 1991 AMS Medinvent S.A. Transluminal Implantation device
5763092, Sep 15 1993 Etex Corporation Hydroxyapatite coatings and a method of their manufacture
5779356, Feb 21 1996 ZIMMER TECHNOLOGY, INC Apparatus and method for mixing first and second components of a bone cement in a vacuum
5782713, Dec 06 1995 Bicycle gear crank arresting device
5782747, Apr 22 1996 ZIMMON, DAVID S Spring based multi-purpose medical instrument
5782830, Feb 20 1996 Warsaw Orthopedic, Inc Implant insertion device
5782838, Oct 20 1994 EV3 PERIPHERAL, INC Cytoscope delivery system
5785647, Jul 31 1996 United States Surgical Corporation Surgical instruments useful for spinal surgery
5785682, Mar 22 1995 HOSPIRA, INC Pre-filled syringe drug delivery system
5792044, Mar 22 1996 SDGI Holdings, Inc Devices and methods for percutaneous surgery
5795922, Jun 06 1995 Clemson University Bone cement composistion containing microencapsulated radiopacifier and method of making same
5797678, Sep 25 1995 Bone cement mixing device and method
5800169, Dec 10 1993 Supply and metering syringe for viscous dental compounds
5800409, Jan 12 1993 CANNUFLOW, INC Flexible inflow/outflow cannula
5800549, Apr 30 1997 Howmedica Osteonics Corp Method and apparatus for injecting an elastic spinal implant
5800550, Mar 13 1996 Interbody fusion cage
5820321, Apr 05 1993 GD-Anker Gruber-Duebel-Anker GmbH Expansion plug with tensioning member and two expansion tubes
5824087, Apr 11 1994 Aberdeen University and Plasma Biotal Limited Bone regeneration
5826713, Oct 31 1994 Fujisawa Pharmaceutical Co., Ltd.; Nissho Corporation Fluid vessel
5826753, Nov 04 1997 Lincoln Industrial Corporation Grease gun locking mechanism
5827217, Sep 04 1996 TISSUE HARVEST SYSTEMS, LLC Process and apparatus for harvesting tissue for processing tissue and process and apparatus for re-injecting processed tissue
5827289, Jan 26 1994 ORTHOPHOENIX, LLC Inflatable device for use in surgical protocols relating to treatment of fractured or diseased bones
5829875, Apr 02 1997 Simpson Strong-Tie Co., Inc. Combined barrier and mixer assembly for a cylindrical container
5830194, Sep 20 1996 LEMAITRE VASCULAR, INC Power syringe
5836306, Dec 23 1994 Medtronic Ave, Inc Exchange accessory for use with a monorail catheter
5839621, Apr 26 1996 MISTLON TECHNOLOGY B V Pump dispenser
5842785, Feb 22 1994 Summit Medical Limited Orthopedic bone cement mixing device with syringe dispenser
5865802, Jul 22 1988 Expandable multifunctional instruments for creating spaces at obstructed sites endoscopically
5876116, Nov 15 1996 ADVANCED BIOMATERIAL SYSTEMS, INC Integrated bone cement mixing and dispensing system
5876457, May 20 1997 George J., Picha Spinal implant
5882340, Apr 15 1992 Penetrating instrument having an expandable anchoring portion for triggering protrusion of a safety member and/or retraction of a penetrating member
5884818, Feb 24 1997 Grease gun
5893488, Sep 18 1995 ZIMMER TECHNOLOGY, INC Bone cement injector gun
5893850, Nov 12 1996 DEPUY SYNTHES PRODUCTS, INC Bone fixation device
5902839, Dec 02 1996 LAUTENSCHLAGER, EUGENE P ; MONAGHAN, PETER, DDS; WIXSON, RICHARD L ; GILBERT, JEREMY L , PH D; DURAY, STEPHEN J Bone cement and method of preparation
5911721, Sep 25 1990 Innovasive Devices, Inc. Bone fastener
5918702, Jun 03 1996 High efficiency grease gun with sealed grease barrel grease-self-absorption
5918770, Feb 27 1995 Dual material dispenser comprising two containers in head to tail arrangement
5925051, Jan 22 1997 Method and apparatus for positioning and compacting bone graft
5928239, Mar 16 1998 Washington, University of Percutaneous surgical cavitation device and method
5931347, May 23 1997 ANDERSON, MARK L , DR Dispenser unit for viscous substances
5941851, Jul 12 1996 C R BARD, INC Pulsed lavage handpiece with improved handle
5954671, Apr 20 1998 2507-PARADIGM BIODEVICES, INC Bone harvesting method and apparatus
5954728, Apr 16 1997 Sulzer Orthopaedie AG Filling apparatus for bone cement
5961211, Nov 15 1996 ADVANCED BIOMATERIAL SYSTEMS, INC Integrated bone cement mixing and dispensing system method
5968008, Aug 04 1997 Cannula with parallel channels and sliding sheath
5968044, Sep 25 1990 Innovasive Devices, Inc. Bone fastener
5968999, Oct 28 1997 CHARLOTTE-MECKLENBURG HOSPITAL AUTHORITY D B A CAROLINAS MEDICAL CENTER Bone cement compositions
5972015, Aug 15 1997 ORTHOPHOENIX, LLC Expandable, asymetric structures for deployment in interior body regions
5980527, May 30 1995 DePuy International Bone cavity sealing assembly
5993535, Aug 28 1997 NGK Spark Plug Co., Ltd. Calcium phosphate cement and calcium phosphate cement composition
5997544, May 02 1997 Biomet Deutschland GmbH Process and device for producing sterile-packed bone cement
6004325, May 11 1998 Biomedical cement bonding enhancement tube
6007496, Dec 30 1996 Syringe assembly for harvesting bone
6017349, Jun 05 1997 Sulzer Orthopaedie, AG Transport and processing apparatus for a two-component material
6019765, May 06 1998 DePuy Orthopaedics, Inc Morsellized bone allograft applicator device
6019776, Oct 14 1997 NEUROTHERM, INC Precision depth guided instruments for use in vertebroplasty
6019789, Apr 01 1998 Boston Scientific Scimed, Inc Expandable unit cell and intraluminal stent
6020396, Mar 13 1998 PENN STATE RESEARCH FOUNDATION, THE Bone cement compositions
6022339, Sep 15 1998 Baxter International Inc Sliding reconstitution device for a diluent container
6033105, Nov 15 1996 ADVANCED BIOMATERIAL SYSTEMS, INC Integrated bone cement mixing and dispensing system
6033411, Oct 14 1997 NEUROTHERM, INC Precision depth guided instruments for use in vertebroplasty
6039761, Feb 12 1997 LI MEDICAL TECHNOLOGIES, INC Intervertebral spacer and tool and method for emplacement thereof
6040408, Aug 19 1994 Biomat B.V. Radiopaque polymers and methods for preparation thereof
6041977, Jul 23 1998 Dispensing system for decorating or filling edible products
6042262, Jul 29 1997 Howmedica Osteonics Corp Apparatus for storing, mixing, and dispensing two-component bone cement
6045555, Nov 09 1994 Howmedica Osteonics Corp Bone graft delivery system and method
6048346, Aug 13 1997 ORTHOPHOENIX, LLC Systems and methods for injecting flowable materials into bones
6049026, Jul 03 1996 CLEVELAND CLINIC FOUNDATION, THE Apparatus and methods for preparing an implantable graft
6075067, Aug 15 1994 Corpipharm GmbH & Co Cement for medical use, method for producing the cement, and use of the cement
6080579, Nov 26 1997 Charlotte-Mecklenburg Hospital Authority Method for producing human intervertebral disc cells
6080801, Sep 13 1990 Klaus Draenert Multi-component material and process for its preparation
6080811, Feb 05 1997 BASF Aktiengesellschaft Adhesives for dental prostheses
6083229, Dec 12 1997 Norian Corporation Methods and devices for the preparation, storage and administration of calcium phosphate cements
6086594, Oct 16 1998 Cement pressurizing device
6103779, Apr 26 1995 REINFORCED POLYMERS, INC Method of preparing molding compositions with fiber reinforcement and products obtained therefrom
6116773, Jan 22 1999 Bone cement mixer and method
6120174, Jan 14 1999 ZIMMER TECHNOLOGY, INC Apparatus and method for mixing and dispensing bone cement
6124373, Apr 10 1998 WM MARSH RICE UNIVERSITY Bone replacement compound comprising poly(polypropylene fumarate)
6126689, Jul 30 1998 Trinity Orthopedics, LLC Collapsible and expandable interbody fusion device
6127597, Mar 07 1997 Kyphon SARL Systems for percutaneous bone and spinal stabilization, fixation and repair
6129763, Sep 13 1996 WENZEL SPINE, INC Expandable osteosynthesis cage
6132396, Feb 06 1996 PlasmaSeal LLC Apparatus for applying tissue sealant
6136038, Dec 30 1996 RAAB, SIMON Bone connective prosthesis and method of forming same
6139509, Apr 24 1996 ZIMMER SPINE, INC Graduated bone graft harvester
6142998, Nov 09 1994 Howmedica Osteonics Corp. Bone graft delivery surgical instruments
6146401, Jul 22 1988 Expandable multifunctional instruments for creating spaces at obstructed sites endoscopically
6149651, Jun 02 1997 SDGI Holdings, Inc. Device for supporting weak bony structures
6149655, Dec 12 1997 Norian Corporation Methods and devices for the preparation, storage and administration of calcium phosphate cements
6149664, Aug 27 1998 Micrus Corporation Shape memory pusher introducer for vasoocclusive devices
6160033, Aug 22 1996 Biomet Deutschland GmbH Process for producing bone cement containing active substances
6161955, Sep 12 1996 RADEMAKER B V Device for kneading doughs and pastries
6168597, Feb 28 1996 BIEDERMANN TECHNOLOGIES GMBH & CO KG Bone screw
6174935, Dec 24 1997 GC Corporation Dental adhesive kit
6176607, Jul 29 1997 MOHAMAD ALI HAJIANPOUR Apparatus for dispensing a liquid component of a two-component bone cement and for storing, mixing, and dispensing the cement
6183441, Oct 02 1998 PESCADERO BEACH HOLDINGS CORPORATION Variable rate infusion apparatus with indicator and adjustable rate control
6183516, Oct 08 1998 ZIMMER, INC Method for improved bonding of prosthetic devices to bone
6187015, May 02 1997 Micro Therapeutics, Inc. Expandable stent apparatus and method
6190381, Jun 07 1995 ArthroCare Corporation Methods for tissue resection, ablation and aspiration
6206058, Nov 09 1998 Procter & Gamble Company, The Integrated vent and fluid transfer fitment
6210031, Jan 22 1999 Bone cement device and package
6214012, Nov 13 1998 SPINE BY DESIGN, LLC Method and apparatus for delivering material to a desired location
6214016, Apr 29 1999 Medtronic, Inc. Medical instrument positioning device internal to a catheter or lead and method of use
6214037, Mar 18 1999 FOSSA MEDICAL INC Radially expanding stent
6217566, Oct 02 1997 Target Therapeutics, Inc Peripheral vascular delivery catheter
6217581, Oct 18 1995 High pressure cement injection device for bone repair
6217608, Mar 05 1996 Evysio Medical Devices ULC Expandable stent and method for delivery of same
6221029, May 13 1999 Stryker Corporation Universal biopsy system
6224604, Jul 30 1999 Expandable orthopedic drill for vertebral interbody fusion techniques
6228049, Feb 09 1996 Promex Technologies, LLC Surgical and pharmaceutical site access guide and methods
6228068, May 22 1996 Expandable endoscopic portal and methods therefor
6228082, Nov 25 1997 ArthroCare Corporation Systems and methods for electrosurgical treatment of vascular disorders
6231615, Oct 14 1997 NEUROTHERM, INC Enhanced visibility materials for implantation in hard tissue
6235043, Jan 26 1994 ORTHOPHOENIX, LLC Inflatable device for use in surgical protocol relating to fixation of bone
6238399, Sep 16 1998 Sulzer Orthopaedie AG Filling transfer apparatus for bone cement
6241734, Aug 14 1998 ORTHOPHOENIX, LLC Systems and methods for placing materials into bone
6245101, May 03 1999 FEMORALIS, LLC Intravascular hinge stent
6248110, Jan 26 1994 ORTHOPHOENIX, LLC Systems and methods for treating fractured or diseased bone using expandable bodies
6254268, Jul 16 1999 Depuy Orthopaedics, Inc. Bone cement mixing apparatus
6261289, Oct 26 1998 EXPANDING ORTHOPEDICS, INC Expandable orthopedic device
6264618, Jan 28 1999 FIRST NIAGARA BANK Sampling device and method of retrieving a sample
6264659, Feb 22 1999 NuVasive, Inc Method of treating an intervertebral disk
6264660, Jun 19 1996 ENDOCON GMBH Surgical instrument for mechanical removal of bone cement, and process for production of shock waves
6273916, Oct 22 1999 IZI Medical Products, LLC Method and apparatus for strengthening vertebral bodies
6281271, Apr 24 1998 Ivoclar AG Radically polymerizable dental material
6309395, Nov 09 1994 Howmedica Osteonics Corp. Bone graft delivery surgical instruments
6309420, Oct 14 1997 NEUROTHERM, INC Enhanced visibility materials for implantation in hard tissue
6312149, Feb 26 1999 Biomet Cementing Technologies AB Mixing device
6325812, Mar 05 1993 Covidien LP Trocar system having expandable port
6348055, Mar 24 1999 NEUROTHERM, INC Non-compliant system for delivery of implant material
6348518, Dec 10 1997 Discus Dental, LLC Compositions for making an artificial prosthesis
6350271, May 17 1999 Micrus Corporation Clot retrieval device
6361539, Sep 16 1998 Sulzer Orthopaedie AG Filling transfer apparatus for bone cement
6364865, Nov 13 1998 Elan Pharma International Limited Drug delivery systems and methods
6367962, Dec 21 1998 NGK SPARK PLUG CO , LTD Device and method for preparing calcium phosphate-based bone cement
6375659, Feb 20 2001 ORTHOVITA, INC Method for delivery of biocompatible material
6375682, Aug 06 2001 X-Pantu-Flex DRD Limited Liability Company Collapsible, rotatable and expandable spinal hydraulic prosthetic device
6383188, Feb 15 2000 SPINEOLOGY INC Expandable reamer
6383190, Apr 01 1998 NEUROTHERM, INC High pressure applicator
6395007, Mar 16 1999 ZIMMER BIOMET SPINE, INC Apparatus and method for fixation of osteoporotic bone
6402701, Mar 23 1999 FNA Concepts, LLC Biopsy needle instrument
6402758, Apr 16 2001 Methods for repairing bone using a high pressure cement injection
6406175, May 04 2000 Bone cement isovolumic mixing and injection device
6409972, Jun 06 1995 ZIMMER TECHNOLOGY, INC Prepackaged liquid bone cement
6410612, Mar 03 1999 KURARAY NORITAKE DENTAL INC Denture rebases
6425887, Dec 09 1998 Cook Medical Technologies LLC Multi-directional needle medical device
6431743, Oct 06 1999 NGK SPARK PLUG CO , LTD Method of preparing and extruding a chemical agent using a kneader and chemical-agent extrusion assisting tool
6433037, Apr 26 1995 Reinforced Polymers, Inc. Method of preparing molding compositions with fiber reinforcement and products obtained therefrom
6436143, Feb 22 1999 NuVasive, Inc Method and apparatus for treating intervertebral disks
6439439, Jan 12 2001 Telios Orthopedic Systems, Inc Bone cement delivery apparatus and hand-held fluent material dispensing apparatus
6443334, Apr 10 2001 PENTALPHA MACAU COMMERCIAL OFFSHORE LTD Comestible fluid dispenser apparatus and method
6447478, May 15 1998 Thin-film shape memory alloy actuators and processing methods
6450973, Jun 16 2000 IZI Medical Products, LLC Biopsy gun
6458117, Jan 19 2000 Intraosseous infusion assembly and method for intraosseous infusion
6479565, Aug 16 1999 Bioactive ceramic cement
6488667, Jun 15 2000 IZI Medical Products, LLC Needle control device
6494868, Apr 27 2000 Set of cannulae for tissue injections in the human face
6500182, Mar 27 1998 COOK UROLOGICAL INC Minimally-invasive medical retrieval device
6502608, Feb 14 2000 Telios Orthopedic Systems, Inc Delivery apparatus, nozzle, and removable tip assembly
6527144, Jul 06 2000 APTAR RADOLFZELL GMBH Discharge apparatus for media
6550957, Oct 07 1999 NGK Spark Plug Co., Ltd. Device and method for preparing calcium phosphate-based cement
6554833, Oct 26 1998 EXPANDING ORTHOPEDICS INC Expandable orthopedic device
6568439, Apr 20 1999 JMS Co., Ltd. Container cap and liquid communication adapter
6572256, Oct 09 2001 ADVANCED BIOMATERIAL SYSTEMS, INC Multi-component, product handling and delivering system
6575331, Dec 14 2001 Nordson Corporation Hydraulically and volumetrically dispensing and filling fluid
6575919, Oct 19 1999 ORTHOPHOENIX, LLC Hand-held instruments that access interior body regions
6582439, Dec 28 2001 PAUBO, LLC Vertebroplasty system
6592559, Dec 09 1998 Cook Medical Technologies LLC Hollow, curved, superlastic medical needle
6595967, Feb 01 2001 ZOLL CIRCULATION, INC Collapsible guidewire lumen
6599293, Jul 16 2001 Stryker Instruments Delivery device for bone cement
6599520, Oct 14 1999 Warsaw Orthopedic, Inc Method of inducing new bone growth in porous bone sites
6613018, Feb 20 2001 ORTHOVITA, INC System and kit for delivery of restorative materials
6613054, Aug 14 1998 ORTHOPHOENIX, LLC Systems and methods for placing materials into bone
6626912, Nov 21 2000 STRYKER EUROPEAN HOLDINGS III, LLC Process for mixing and dispensing a flowable substance
6641587, Aug 14 1998 ORTHOPHOENIX, LLC Systems and methods for treating vertebral bodies
6645213, Aug 13 1997 ORTHOPHOENIX, LLC Systems and methods for injecting flowable materials into bones
6662969, Dec 14 2001 Nordson Corporation Hydraulically and volumetrically dispensing a target fluid
6676664, Aug 05 1999 GRIFOLS, S A ; GRIFOLS S A Device for metering hardenable mass for vertebroplastia and other similar bone treatments
6689823, Mar 31 1999 BRIGHAM AND WOMEN S HOSPITAL, INC , THE Nanocomposite surgical materials and method of producing them
6702455, Dec 01 2000 DEPUY SYNTHES PRODUCTS, INC Bone cement mixing apparatus having improved gearing arrangement for driving a mixing blade
6712853, Dec 15 2000 Spineology, Inc.; SPINEOLOGY, INC Annulus-reinforcing band
6716216, Aug 14 1998 ORTHOPHOENIX, LLC Systems and methods for treating vertebral bodies
6719761, Aug 13 1997 ORTHOPHOENIX, LLC System and methods for injecting flowable materials into bones
6720417, Jan 28 1997 Roche Diagnostics GmbH Method and device for refining nucleic acids
6730095, Jun 26 2002 Boston Scientific Scimed, Inc Retrograde plunger delivery system
6752180, Sep 17 2001 PEROUSE MEDICAL Device for the bidirectional transfer of a liquid between a vial and a carpule
6758837, Feb 08 2001 Pharmacia AB Liquid delivery device and method of use thereof
6759449, Nov 28 2000 Tokuyama Dental Corporation; Tokuyama Corporation Dental adhesive composition
6767973, Dec 27 1999 Coatex S.A.S. Use of water soluble polymers as dispersion agent of aqueous calcium carbonate suspension, resulting aqueous suspensions and their uses
6770079, Mar 16 1999 ZIMMER BIOMET SPINE, INC Apparatus and method for fixation of osteoporotic bone
6779566, Jan 14 2003 Access Business Group International LLC Connector device for sealing and dispensing freeze-dried preparations
6780175, Feb 23 1996 EVM Systems LLC Medical instrument with slotted memory metal tube
6783515, Sep 30 1999 NEUROTHERM, INC High pressure delivery system
6787584, Aug 11 2000 Pentron Corporation Dental/medical compositions comprising degradable polymers and methods of manufacture thereof
6796987, Jul 16 2001 Stryker Instruments Delivery device for bone cement
6852439, May 15 2001 7188501 CANADA INC ; Hydrogenics Corporation Apparatus for and method of forming seals in fuel cells and fuel cell stacks
6874927, Jan 31 2000 Summit Medical Limited Orthopaedic cement mixing and dispensing device
6875219, Feb 14 2003 NEUROTHERM, INC Bone access system
6887246, Mar 16 1999 ZIMMER BIOMET SPINE, INC Apparatus and method for fixation of osteoporotic bone
6916308, Jun 08 2000 IZI Medical Products, LLC High pressure injection syringe
6957747, Dec 14 2001 Nordson Corporation Hydraulically and volumetrically dispensing fluid
6974247, Apr 11 2002 Synthes USA, LLC Device for mixing and/or injecting cements
6974416, Aug 16 2000 Cook Medical Technologies LLC Doppler probe with shapeable portion
6979341, Jan 26 1994 ORTHOPHOENIX, LLC Expandable preformed structures for deployment in interior body regions
6979352, Nov 21 2002 DePuy Acromed Methods of performing embolism-free vertebroplasty and devices therefor
6994465, Mar 14 2002 Stryker Corporation Mixing assembly for mixing bone cement
6997930, Jun 30 2000 Synthes USA, LLC Device for injecting bone cement
7008433, Feb 15 2001 DEPUY ACROMED, INC Vertebroplasty injection device
7025771, Jun 30 2000 SPINEOLOGY, INC Tool to direct bone replacement material
7029163, Apr 17 2002 Globus Medical, Inc Apparatus for mixing and dispensing components
7044954, Jan 26 1994 ORTHOPHOENIX, LLC Method for treating a vertebral body
7048743, Sep 30 1999 NEUROTHERM, INC Methods for delivering tissue implant material with a high pressure applicator
7066942, Oct 03 2003 Wright Medical Technology, Inc. Bendable needle for delivering bone graft material and method of use
7087040, Feb 28 2001 Rex Medical, L.P. Apparatus for delivering ablation fluid to treat lesions
7091258, Feb 21 2001 Ivoclar Vivadent AG Filler on the basis of particulate composite
7097648, Jan 27 1999 Kyphon SARL Expandable element delivery system
7112205, Jun 17 2003 Boston Scientific Scimed, Inc Apparatus and methods for delivering compounds into vertebrae for vertebroplasty
7116121, Oct 27 2005 Agilent Technologies Inc Probe assembly with controlled impedance spring pin or resistor tip spring pin contacts
7252671, Aug 14 1998 ORTHOPHOENIX, LLC Systems and methods for treating vertebral bodies
7264622, Jun 10 1993 Warsaw Orthopedic, Inc System for radial bone displacement
7270667, Jun 26 2002 TECRES SpA Device for the manual metering of a medical fluid, particularly bone cement
7278778, Oct 25 2000 Kyphon SARL System for mixing and transferring flowable materials
7320540, Jul 16 2001 Stryker Corporation Bone cement mixing and delivery device with releasable mixing blade
7326203, Sep 30 2002 Depuy Acromed, Inc.; DePuy Acromed Device for advancing a functional element through tissue
7456024, Aug 29 2001 DR DR MICHAEL W DAHM Method and device for preparing a sample of biological origin in order to determine at least one constituent contained therein
7470258, Mar 13 2001 MDC INVESTMENT HOLDINGS, INC Pre-filled safety vial injector
7559932, Dec 06 2004 DFINE, INC.; DFINE, INC Bone treatment systems and methods
7572263, Apr 01 1998 NEUROTHERM, INC High pressure applicator
7604618, Jun 08 2000 IZI Medical Products, LLC High pressure injection syringe
7666205, Apr 19 2001 Synthes USA, LLC Inflatable device and method for reducing fractures in bone and in treating the spine
7678116, Dec 06 2004 DFINE, INC.; DFINE, INC Bone treatment systems and methods
7717918, Dec 06 2004 DFINE, INC Bone treatment systems and methods
7722620, Dec 06 2004 DFINE, INC Bone treatment systems and methods
8038682, Aug 17 2004 Boston Scientific Scimed, Inc Apparatus and methods for delivering compounds into vertebrae for vertebroplasty
8066713, Mar 31 2003 DePuy Synthes Products, LLC Remotely-activated vertebroplasty injection device
8070753, Dec 06 2004 DFINE, INC Bone treatment systems and methods
817973,
833044,
8333773, Mar 31 2003 DePuy Synthes Products, LLC Remotely-activated vertebroplasty injection device
8360629, Nov 22 2005 DePuy Synthes Products, LLC Mixing apparatus having central and planetary mixing elements
8361078, Jun 17 2003 DePuy Synthes Products, LLC Methods, materials and apparatus for treating bone and other tissue
8415407, Jul 30 2004 DePuy Synthes Products, LLC Methods, materials, and apparatus for treating bone and other tissue
843587,
8540722, Jun 17 2003 DePuy Synthes Products, LLC Methods, materials and apparatus for treating bone and other tissue
8809418, Mar 21 2004 DePuy Synthes Products, LLC Methods, materials and apparatus for treating bone and other tissue
8950929, Oct 19 2006 DePuy Synthes Products, LLC Fluid delivery system
8956368, Jun 17 2003 DePuy Synthes Products, LLC Methods, materials and apparatus for treating bone and other tissue
9186194, Mar 14 2003 DEPUY SYNTHES PRODUCTS, INC. Hydraulic device for the injection of bone cement in percutaneous vertebroplasty
9259696, Nov 22 2005 DEPUY SYNTHES PRODUCTS, INC Mixing apparatus having central and planetary mixing elements
9381024, Jul 31 2005 DEPUY SYNTHES PRODUCTS, INC Marked tools
9504508, Jun 17 2003 DEPUY SYNTHES PRODUCTS, INC. Methods, materials and apparatus for treating bone and other tissue
20010012968,
20010024400,
20010034527,
20020008122,
20020010471,
20020010472,
20020013553,
20020049448,
20020049449,
20020058947,
20020067658,
20020068939,
20020068974,
20020068975,
20020072768,
20020082605,
20020099384,
20020099385,
20020118595,
20020123716,
20020156483,
20020161373,
20020177866,
20020183851,
20020188300,
20020191487,
20030009177,
20030018339,
20030031698,
20030032929,
20030036763,
20030040718,
20030050644,
20030050702,
20030078589,
20030109883,
20030109884,
20030144742,
20030162864,
20030174576,
20030181963,
20030185093,
20030220414,
20030225364,
20030227816,
20030231545,
20040010263,
20040029996,
20040054377,
20040059283,
20040066706,
20040068264,
20040073139,
20040092946,
20040098015,
20040106913,
20040122438,
20040132859,
20040133124,
20040133211,
20040138759,
20040157952,
20040157954,
20040162559,
20040167532,
20040167562,
20040167625,
20040193171,
20040215202,
20040220672,
20040226479,
20040229972,
20040230309,
20040236313,
20040249015,
20040249347,
20040260303,
20040260304,
20040267154,
20050014273,
20050015148,
20050025622,
20050058717,
20050060023,
20050070912,
20050070914,
20050070915,
20050083782,
20050113762,
20050143827,
20050154081,
20050180806,
20050203206,
20050209695,
20050216025,
20050256220,
20050281132,
20060035997,
20060041033,
20060052794,
20060074433,
20060079905,
20060116643,
20060116689,
20060116690,
20060122614,
20060148923,
20060167148,
20060181959,
20060235338,
20060241644,
20060264695,
20060264967,
20060266372,
20060271061,
20060276819,
20070027230,
20070032567,
20070055266,
20070055267,
20070055278,
20070055280,
20070055284,
20070055285,
20070055300,
20070060941,
20070118142,
20070142842,
20070197935,
20070198013,
20070198023,
20070198024,
20070255282,
20070282443,
20080039856,
20080044374,
20080058827,
20080065087,
20080065089,
20080065137,
20080065142,
20080065190,
20080071283,
20080086133,
20080132935,
20080140079,
20080140084,
20080200915,
20080212405,
20080228192,
20090264892,
20090264942,
20090270872,
20100065154,
20100069786,
20100152855,
20100168271,
20100268231,
20120307586,
20130123791,
20130261217,
20130345708,
20140088605,
20140148866,
20150122691,
20150127058,
20150148777,
20160051302,
AU724544,
AU9865136,
CN1138001,
CN1310026,
D279499, Feb 18 1983 Zimmer, Inc. Mixing apparatus
DE10258140,
DE1283448,
DE136018,
DE1810799,
DE19612276,
DE226956,
DE2821785,
DE293485,
DE2947875,
DE3003947,
DE3443167,
DE3730298,
DE3817101,
DE4016135,
DE4104092,
DE4315757,
DE868497,
DE8716073,
EP44877,
EP177781,
EP190504,
EP235905,
EP242672,
EP301759,
EP423916,
EP425200,
EP475077,
EP493789,
EP511868,
EP581387,
EP614653,
EP669100,
EP748615,
EP763348,
EP1074231,
EP1095667,
EP1103237,
EP1104260,
EP1148850,
EP1148851,
EP1247454,
EP1464292,
EP1517655,
EP1552797,
EP1570873,
EP1596896,
EP1598015,
EP1829518,
EP1886647,
EP1886648,
EP20207,
EP486638,
FR1548575,
FR2606282,
FR2629337,
FR2638972,
FR2674119,
FR2690332,
FR2712486,
FR2722679,
GB179502045,
GB190720207,
GB2114005,
GB2156824,
GB2197691,
GB2268068,
GB2276560,
GB2411849,
GB2413280,
GB2469749,
GB408668,
GB486638,
GB8331,
JP10146559,
JP10511569,
JP2001514922,
JP200416707,
JP2005500103,
JP200855367,
JP2122017,
JP2125730,
JP2166235,
JP4329956,
JP51134465,
JP54009110,
JP55009242,
JP55109440,
JP62068893,
JP63194722,
JP7000410,
JP8322848,
RO116784,
RU1011119,
RU1049050,
SU662082,
WO2064195,
WO2004080357,
WO2005017000,
WO2006062939,
WO8810129,
WO6216,
WO44319,
WO44321,
WO44946,
WO54705,
WO56254,
WO108571,
WO113822,
WO154598,
WO160270,
WO176514,
WO200143,
WO202033,
WO2064062,
WO2064194,
WO2072156,
WO2096474,
WO219933,
WO3007854,
WO3015845,
WO3022165,
WO3061495,
WO3078041,
WO3101596,
WO2004001980,
WO2004002375,
WO2004019810,
WO2004071543,
WO2004075965,
WO2004080357,
WO2004110292,
WO2004110300,
WO2005000138,
WO2005032326,
WO2005048867,
WO2005051212,
WO2005110259,
WO2006011152,
WO2006039159,
WO2006090379,
WO2007015202,
WO2007036815,
WO2007148336,
WO2008004229,
WO2008032322,
WO2008047371,
WO9000037,
WO9214423,
WO9412112,
WO9513862,
WO9611643,
WO9619940,
WO9632899,
WO9637170,
WO9718769,
WO9728835,
WO9828035,
WO9838918,
WO9918866,
WO9918894,
WO9929253,
WO9937212,
WO9939661,
WO9949819,
WO9952446,
////////
Executed onAssignorAssigneeConveyanceFrameReelDoc
Sep 11 2007DEPUY SYNTHES PRODUCTS, INC.(assignment on the face of the patent)
Dec 21 2007DISC-O-TECH MEDICAL TECHNOLOGIES LTD Depuy Spine, IncASSIGNMENT OF ASSIGNORS INTEREST SEE DOCUMENT FOR DETAILS 0203700879 pdf
Apr 01 2009BEYAR, MORDECHAYDepuy Spine, IncASSIGNMENT OF ASSIGNORS INTEREST SEE DOCUMENT FOR DETAILS 0230410809 pdf
Apr 01 2009GLOBERMAN, ORENDepuy Spine, IncASSIGNMENT OF ASSIGNORS INTEREST SEE DOCUMENT FOR DETAILS 0230410809 pdf
Dec 30 2012Depuy Spine, IncDEPUY SPINE, LLCCHANGE OF NAME SEE DOCUMENT FOR DETAILS 0303520673 pdf
Dec 30 2012DEPUY SPINE, LLCHAND INNOVATIONS LLCASSIGNMENT OF ASSIGNORS INTEREST SEE DOCUMENT FOR DETAILS 0303520709 pdf
Dec 31 2012HAND INNOVATIONS LLCDePuy Synthes Products, LLCCHANGE OF NAME SEE DOCUMENT FOR DETAILS 0303520722 pdf
Dec 19 2014DePuy Synthes Products, LLCDEPUY SYNTHES PRODUCTS, INCCHANGE OF NAME SEE DOCUMENT FOR DETAILS 0350740647 pdf
Date Maintenance Fee Events
Oct 02 2020M1551: Payment of Maintenance Fee, 4th Year, Large Entity.


Date Maintenance Schedule
May 09 20204 years fee payment window open
Nov 09 20206 months grace period start (w surcharge)
May 09 2021patent expiry (for year 4)
May 09 20232 years to revive unintentionally abandoned end. (for year 4)
May 09 20248 years fee payment window open
Nov 09 20246 months grace period start (w surcharge)
May 09 2025patent expiry (for year 8)
May 09 20272 years to revive unintentionally abandoned end. (for year 8)
May 09 202812 years fee payment window open
Nov 09 20286 months grace period start (w surcharge)
May 09 2029patent expiry (for year 12)
May 09 20312 years to revive unintentionally abandoned end. (for year 12)